# 0

**SMILES:** C1=CC=C(C(=C1)C2=NC=CC(=N2)N3C=CN=C3)Cl

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a chlorophenyl group contributes to the lipophilic nature of the molecule. Chlorine atoms increase lipophilicity due to their electron-withdrawing properties, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The pyrimidine and imidazole rings introduce some degree of polarity to the molecule. However, the overall polarity is balanced by the lipophilic chlorophenyl group, suggesting moderate polarity. This balance can favor moderate permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The aromatic rings, such as the phenyl and pyrimidine rings, contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can also influence the molecule's lipophilicity and its ability to interact with the membrane through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of multiple aromatic rings and heteroatoms (such as nitrogen in pyrimidine and imidazole) suggests that the molecule may have a moderate hydration energy. This can affect its solubility and permeability, potentially leading to moderate permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, molecular size, and polarity, along with the presence of aromatic and heterocyclic rings, suggests that while it can interact with the membrane, its size and structural complexity may limit its permeability compared to smaller or less complex molecules.

Final answer: Low-to-moderate permeability

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# 1

**SMILES:** CC1=NC(=NC2=CC=CC=C12)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of quinazoline, which is a bicyclic compound consisting of a benzene ring fused to a pyrimidine ring. The presence of the quinazoline core contributes to the molecule's aromaticity, which can enhance its lipophilicity and ability to interact with lipid membranes.

The molecule also features a methyl group attached to the quinazoline structure. This methyl group increases the lipophilicity of the molecule, potentially enhancing its permeability through the lipid bilayer of the artificial membrane.

Additionally, the molecule contains an amine group, which can participate in hydrogen bonding. However, the amine group is not a strong hydrogen bond donor or acceptor, which may not significantly hinder the molecule's permeability. The presence of this group can also contribute to the molecule's overall polarity, but its impact is likely minimal compared to the lipophilic characteristics imparted by the quinazoline and methyl groups.

Overall, the given molecule's structure suggests that it would have high permeability in the Parallel Artificial Membrane Permeability Assay due to its aromaticity, lipophilicity, and moderate polarity.

Final answer: High permeability

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# 2

**SMILES:** C1=NC(=C2C(=N1)N(C=N2)[C@@H]3[C@@H]([C@@H]([C@@H](O3)CO)O)N)N

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a nucleoside analogue, specifically a modified adenosine. Its structure includes a purine base, which is a common feature in nucleosides, linked to a sugar moiety. This sugar moiety is a ribose derivative, which is characterized by the presence of amino and hydroxymethyl groups.

Analyzing the properties:

1. **Lipophilicity**: The purine base contributes to the molecule's lipophilicity, while the hydroxymethyl group and amino groups introduce some hydrophilicity. The balance between these properties suggests moderate lipophilicity, which is typical for nucleoside analogues.

2. **Molecular Size and Weight**: The given molecule is relatively small, which is common for nucleosides. This size allows it to traverse biological membranes effectively.

3. **Polarity**: The presence of amino groups and hydroxyl groups contributes to the molecule's polarity. However, the purine base and the overall structure still maintain a balance that allows for moderate permeability.

4. **Charge**: The molecule is neutral at physiological pH, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The purine base and the sugar ring provide a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The purine base contains aromatic rings, which can enhance lipophilicity and facilitate interactions with the lipid bilayer.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule has a moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic properties suggests that the given molecule has a balanced affinity for both the aqueous and lipid phases, which is advantageous for membrane permeability.

Overall, the given molecule exhibits a combination of properties that favor moderate permeability in the PAMPA assay, making it suitable for further biological evaluation.

Final answer: Low-to-moderate permeability

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# 3

**SMILES:** CN1CCC2=CC(=C3C4=C2[C@H]1CC5=CC=C(C=C5)OC6=C(C=CC(=C6)C[C@H]7C8=CC(=C(O3)C=C8CCN7)O4)OC)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex polycyclic compound with multiple rings and heteroatoms, including oxygen and nitrogen. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of multiple aromatic rings and ether linkages suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is quite large and complex, with a significant number of rings and heteroatoms. This size can potentially hinder permeability due to steric effects, which may limit its ability to pass through the membrane.

3. **Polarity**: The molecule contains ether and methoxy groups, which contribute to its polarity. However, the overall structure is dominated by aromatic and hydrocarbon components, suggesting that the polar surface area is not high enough to significantly impede permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The polycyclic structure of the given molecule suggests a high degree of rigidity. This rigidity can facilitate permeability as it allows the molecule to maintain a stable conformation while interacting with the membrane.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of ether and methoxy groups may lower the hydration energy of the molecule, making it easier for the molecule to permeate the membrane by reducing the energy required to escape from the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule's lipophilicity, rigidity, and balanced polarity suggest that it would have high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

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# 4

**SMILES:** C1=CC2=C(C=C1I)C(=CC3=CC(=C(C(=C3)Br)O)Br)C(=O)N2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of bromine atoms and aromatic rings in the structure suggests a relatively high lipophilicity. Bromine atoms increase the molecule's hydrophobic character, which can enhance its ability to permeate lipid membranes.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the pores of the artificial membrane.

3. **Polarity**: The hydroxyl group on the phenyl ring introduces some polarity, which can affect the molecule's solubility and permeability. However, the overall structure is dominated by hydrophobic aromatic rings and bromine atoms, suggesting that the molecule's polarity is not a significant barrier to permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indole moiety and aromatic rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of hydroxyl and bromine groups may lower the hydration energy of the molecule, making it easier for the molecule to permeate the membrane by reducing the energy required to escape from the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and balanced polarity.

Final answer: High permeability

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# 5

**SMILES:** COC(=O)NC1=NC2=C(N1)C=C(C=C2)C(=O)C3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a benzimidazole derivative, which is a class of compounds known for their biological activity and potential pharmaceutical applications. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of a benzoyl group attached to the benzimidazole core increases the lipophilicity of the molecule. This group is a hydrophobic aromatic moiety, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The benzimidazole core is relatively small, and the addition of the benzoyl group and the carbamate moiety does not significantly increase the overall molecular size. This suggests that the molecule should have sufficient permeability due to its relatively compact structure.

3. **Polarity**: The carbamate group introduces some polarity to the molecule, but the overall structure is dominated by the hydrophobic benzoyl and benzimidazole rings. This balance of hydrophobic and polar regions can facilitate membrane permeation by allowing the molecule to interact with both the lipid bilayer and the aqueous environment.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The benzimidazole and benzoyl groups contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by reducing the flexibility and conformational changes required for passage through the lipid bilayer.

6. **Aromaticity**: The aromatic rings present in the benzoyl and benzimidazole groups can engage in π-π interactions with the lipid bilayer, potentially enhancing the molecule's affinity for the membrane and its permeability.

7. **Hydration Energy**: The presence of both hydrophobic and hydrophilic regions in the molecule suggests that it may have a moderate hydration energy, which can influence its permeability by balancing solubility in the aqueous phase and interaction with the lipid phase.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties, along with the structural features, suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typically desirable for good permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, structural rigidity, and aromaticity, as well as its neutral charge and moderate polarity.

Final answer: High permeability

------
# 6

**SMILES:** C[C@@]12C3=CC=CC=C3C[C@@H](N1)C4=CC=CC=C24

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex polycyclic compound with several notable structural features that influence its permeability in the PAMPA assay. 

Firstly, the molecule's polycyclic structure, characterized by multiple interconnected rings, contributes to its rigidity. This rigidity can enhance its ability to permeate the artificial membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer. 

The presence of aromatic rings within the structure suggests that the molecule has a significant lipophilic character. Aromatic rings can engage in π-π interactions with the lipid components of the membrane, which can facilitate permeation. However, the balance between lipophilicity and other factors will determine the overall permeability.

The molecule is described as a 'tricyclic' compound, indicating three interconnected ring systems. This structural complexity can also contribute to its ability to interact with the membrane, potentially enhancing its permeability due to the unique spatial arrangement of its functional groups.

The azatricyclic component of the molecule introduces a nitrogen atom into the ring system, which can influence the molecule's polarity and hydrogen bonding potential. While the presence of nitrogen can increase polarity, the overall effect on permeability will depend on the balance with other structural features.

The description mentions that the molecule is a 'dihydro' derivative, indicating the presence of additional hydrogen atoms compared to a fully aromatic system. This can slightly increase the polarity and reduce the overall aromatic character, which might affect its permeability by reducing its lipophilicity.

Overall, the given molecule's structural features suggest that it has a balanced combination of rigidity, lipophilicity, and aromaticity, which likely contribute to moderate to high permeability in the PAMPA assay. However, the exact permeability would depend on the specific balance of these factors and how they interact with the artificial membrane.

Final answer: Moderate permeability.

------
# 7

**SMILES:** CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a derivative of folate, specifically a pteridine compound with an amino group and a methyl group attached to the pteridine ring. It also contains a benzoyl group linked to an amino group, and a pentanedioic acid moiety.

Analyzing the properties:

1. **Lipophilicity**: The presence of the pteridine ring and the benzoyl group contributes to the lipophilic nature of the molecule. This suggests that the molecule may have moderate to high lipophilicity, which can enhance its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large due to the presence of multiple functional groups and aromatic rings. This size can potentially limit its permeability, as larger molecules may have difficulty traversing the lipid bilayer.

3. **Polarity**: The molecule contains several polar groups, including amino groups and carboxylic acid groups. However, the overall polarity is balanced by the lipophilic aromatic and pteridine rings, which may allow for moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can interact with the lipid bilayer without being repelled by charge.

5. **Rigidity**: The aromatic rings and the pteridine structure contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by maintaining a stable conformation.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can influence its interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these properties, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay.

Final answer: Moderate permeability.

------
# 8

**SMILES:** C1COCCN1C2=C(C=C(C=C2)C(F)(F)F)NC(=O)C3=NNC(=O)C4=CC=CC=C43

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and morpholine-containing phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, as indicated by its molecular weight. Large molecules often have reduced permeability due to size limitations in passing through the membrane. However, the specific arrangement of functional groups and the rigidity of the structure can influence this.

3. **Polarity**: The morpholine ring introduces a degree of polarity, which can affect the molecule's solubility and permeability. The presence of a trifluoromethyl group also adds to the molecule's lipophilicity, potentially offsetting the polar effects of the morpholine.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The phthalazine moiety contributes to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and conformational changes that might hinder passage.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially aiding in permeation.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability.

Considering these properties, the given molecule is likely to exhibit high permeability in the artificial membrane due to its lipophilic nature, aromaticity, and balanced polarity.

Final answer: High permeability

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# 9

**SMILES:** CCCCCN1C(=O)C2=C(C=C(C=C2)C(=O)NCCCN3CCCCC3)NC1=O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinazoline derivative, which is a class of compounds known for their diverse biological activities. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the quinazoline core, which is a bicyclic aromatic system, contributes to the lipophilicity of the molecule. Additionally, the butyl and piperidinylpropyl groups further enhance its lipophilic character. These hydrophobic groups can increase the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular size and weight due to the quinazoline core and the attached functional groups. While size is generally a limiting factor for permeability, the presence of aromatic rings and flexible alkyl chains can mitigate this effect by allowing the molecule to fit into the membrane's lipid bilayer.

3. **Polarity**: The molecule contains a carboxamide group, which introduces some polarity. However, the overall polarity is balanced by the extensive hydrophobic regions, such as the quinazoline core and alkyl chains. This balance suggests moderate polarity, which is suitable for membrane permeation.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The quinazoline core provides a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The quinazoline structure contributes to the aromaticity of the molecule, which can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the carboxamide, may lead to moderate hydration energy. However, the overall hydrophobic character of the molecule suggests that it may have lower hydration energy, which can enhance membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is advantageous for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, balanced polarity, and favorable interactions with the artificial membrane.

Final answer: High permeability

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# 10

**SMILES:** CC1=C(C(=NO1)C2=CC=CC=C2)C(=O)NC3=NN=C(S3)COC4=CC=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and chlorophenoxy groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule has a moderate molecular size and weight, which is typical for many bioactive compounds. While larger molecules can have reduced permeability due to size constraints, the specific structure of this molecule suggests it may still have sufficient permeability.

3. **Polarity**: The molecule contains a carboxamide group, which can contribute to polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting that the polar surface area is not excessively high, which could favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The presence of the 1,3,4-thiadiazole ring and the aromatic systems contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also can participate in π-π interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the chlorophenoxy group and the overall structure of the molecule suggest that it may have a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable membrane affinity, which is essential for permeability in the PAMPA assay.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, neutral charge, and favorable membrane interactions.

Final answer: High permeability

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# 11

**SMILES:** C1OC2=C(O1)C=C(C=C2)C3NN4C(=NN=C4S3)C5=CC=CC=C5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzodioxole and triazolothiadiazole moieties, contributes to the lipophilic character of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the specific arrangement of the aromatic and heterocyclic rings might allow for some flexibility and conformational adaptability, potentially mitigating this effect.

3. **Polarity**: The molecule contains a benzodioxole group, which can contribute to its overall polarity. However, the presence of multiple aromatic rings and heteroatoms (such as nitrogen and sulfur) may balance this, resulting in a moderate polar surface area. This balance can favor moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to traverse lipid membranes.

5. **Rigidity**: The aromatic and heterocyclic rings impart a degree of rigidity to the molecule. While rigidity can sometimes hinder permeability due to limited conformational flexibility, the specific arrangement of these rings might allow for favorable interactions with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of multiple heteroatoms and aromatic rings suggests that the molecule may have a lower hydration energy, which can enhance its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a favorable affinity for both the aqueous and lipid phases, which is generally beneficial for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, moderate polarity, and favorable interactions with the lipid bilayer.

Final answer: High permeability

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# 12

**SMILES:** COC1=CC2=C(C=C1)NC(=O)C(=C2)C3=NOC(=N3)C4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a member of the quinoline class, which is known for its diverse biological activities and potential pharmaceutical applications. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the methoxy group and the quinoline moiety contributes to the lipophilic character of the molecule. Quinoline derivatives are generally lipophilic, which can enhance membrane permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings, including a quinoline and a 1,2,4-oxadiazole ring. While these rings contribute to the molecular weight, the overall size is still manageable, which may not significantly hinder permeability.

3. **Polarity**: The methoxy group and the oxadiazole ring introduce some polarity, but the overall structure is dominated by aromatic and heterocyclic components, which are less polar. This suggests moderate polarity, which is balanced by the lipophilic nature of the quinoline.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic and heterocyclic rings impart a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing conformational flexibility.

6. **Aromaticity**: The quinoline and phenyl groups contribute to the aromatic character, which can enhance lipophilicity and facilitate interactions with the lipid bilayer.

7. **Hydration Energy**: The presence of polar groups and aromatic rings suggests that the hydration energy is moderate, which may allow the molecule to interact with both the aqueous and lipid phases effectively.

8. **Membrane Affinity**: The balance of lipophilic and polar characteristics suggests that the given molecule has a favorable membrane affinity, which is essential for high permeability in the PAMPA assay.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, moderate polarity, and structural rigidity.

Final answer: High permeability

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# 13

**SMILES:** CC1=CC=CC=C1C2=NC(=C(O2)C)CN3CCC(CC3)C(=O)NCCCN4CCOCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methyl groups and aromatic rings, such as the phenyl and oxazole rings, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.5 g/mol. While size is a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help to maintain some degree of rigidity, which can improve permeability by allowing the molecule to fit into the membrane more easily.

3. **Polarity**: The molecule contains a carboxamide group, which can contribute to polarity. However, the overall polarity is balanced by the lipophilic aromatic and methyl groups, suggesting that the polar surface area is not excessively high, which is favorable for permeability.

4. **Charge**: The given molecule is neutral, as it does not contain any charged functional groups. This neutrality is beneficial for permeability, as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The oxazole ring and the phenyl ring contribute to the rigidity of the molecule. This rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings in the structure can engage in π-π interactions with the lipid bilayer, which may enhance permeability. However, the presence of these rings also contributes to the overall lipophilicity, which is favorable for permeability.

7. **Hydration Energy**: The presence of polar groups, such as the carboxamide, suggests that the molecule may have moderate hydration energy. This can influence its solubility and permeability, with lower hydration energy generally improving membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typically desirable for good permeability in PAMPA assays.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, balanced polarity, neutral charge, and structural rigidity.

Final answer: High permeability

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# 14

**SMILES:** C1=CC(=CN=C1)NC(=O)C2=CC=CS2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which consists of a thiophene ring and a pyridine ring connected through a carboxamide linkage. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of aromatic rings, such as the thiophene and pyridine, contributes to the molecule's lipophilicity. Aromatic rings are known to enhance lipophilicity, which can improve membrane permeability up to a certain point.

2. **Molecular Size and Weight**: The given molecule is relatively small, which is beneficial for permeability. Smaller molecules generally have higher permeability as they can more easily pass through the lipid bilayer.

3. **Polarity**: The pyridine ring introduces some degree of polarity due to its nitrogen atom, which can participate in hydrogen bonding. However, the overall polarity is balanced by the lipophilic thiophene ring, which may not significantly hinder permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability. Charged molecules often have reduced permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation while interacting with the membrane.

6. **Aromaticity**: The aromatic nature of the thiophene and pyridine rings can facilitate interactions with the lipid bilayer, potentially enhancing permeability through π-π interactions with the membrane's phospholipids.

7. **Hydration Energy**: The aromatic and amide groups may have moderate hydration energy, which can influence the molecule's ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance between the hydrophilic and hydrophobic parts of the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, size, and structural rigidity, as well as its ability to interact with the lipid bilayer.

Final answer: High permeability

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# 15

**SMILES:** CC1=CC=CC=C1NC(=O)NC2=CC=CS2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of urea, featuring a 2-methylphenyl group and a thiophen-2-yl group. Let's analyze its properties to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the 2-methylphenyl group contributes to the lipophilic nature of the molecule. This aromatic ring can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively small, which generally favors higher permeability. The urea linkage and the thiophene ring contribute to a compact molecular framework, which can facilitate diffusion through the membrane.

3. **Polarity**: The urea moiety introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic rings. The low polar surface area and the presence of hydrogen bond donors and acceptors in the urea group suggest moderate polarity, which may not hinder permeability significantly.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings and the urea linkage provide a degree of rigidity to the molecule. This rigidity can enhance its ability to interact with the membrane, potentially improving permeability.

6. **Aromaticity**: The thiophene ring and the phenyl group contribute to the aromatic character of the molecule. Aromaticity can influence the molecule's ability to insert into the lipid bilayer, affecting permeability.

7. **Hydration Energy**: The presence of aromatic and heteroaromatic rings may lower the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance between hydrophobic and hydrophilic interactions in the given molecule suggests a favorable membrane affinity, which is conducive to higher permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, and structural rigidity.

Final answer: High permeability

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# 16

**SMILES:** C1=NC2=C(N1)C(=O)NC=N2

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a derivative of purine, specifically a 7-deazapurine. This molecule is characterized by the absence of a nitrogen atom at the 7-position, which is a key structural feature that influences its chemical properties and biological interactions.

1. **Lipophilicity**: The absence of a nitrogen atom at the 7-position reduces the overall polarity of the molecule compared to standard purine. This decrease in polarity can enhance lipophilicity, which generally correlates with increased permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule is relatively small, which can contribute to its permeability. Smaller molecules typically have higher permeability due to their ability to traverse biological membranes more easily.

3. **Polarity**: The molecule has a low polar surface area, which is a result of the deazination at the 7-position. This low polar surface area can enhance its ability to interact with the hydrophobic environment of the lipid bilayer, thus improving permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability. Neutral molecules are generally more likely to diffuse through the lipid bilayer than charged species, which are often hindered by the hydrophobic nature of the membrane.

5. **Rigidity**: The presence of a purine ring system imparts a degree of rigidity to the molecule. This rigidity can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The purine ring system is aromatic, which can influence the molecule's lipophilicity and interactions with the lipid bilayer. Aromaticity can enhance the ability of the molecule to insert into the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The absence of a nitrogen atom at the 7-position may lower the hydration energy of the molecule. Lower hydration energy can enhance membrane permeation as the molecule is less tightly bound to water molecules, facilitating its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which can contribute to its permeability.

Overall, the structural features of the given molecule, such as its lipophilicity, small size, neutral charge, and aromaticity, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

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# 17

**SMILES:** CC1=CC=C(C=C1)N2C3=NC=NC(=C3C=N2)NC4=CC=CC(=C4)C(=O)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrazolo[3,4-d]pyrimidine and the 4-methylphenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 342.3 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and heterocycles may allow for some degree of flexibility and conformational adaptability, which can mitigate the negative effects of size.

3. **Polarity**: The molecule has a polar surface area of 12.8 sq Å, indicating moderate polarity. The presence of a carboxylic acid group contributes to this polarity, but the overall structure is dominated by the lipophilic aromatic rings, suggesting that the molecule's permeability is more influenced by its lipophilic character.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The aromatic and heterocyclic rings impart a degree of rigidity to the molecule. This rigidity can enhance its ability to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the lipid bilayer, which can enhance permeability.

7. **Hydration Energy**: The hydration energy of the molecule is relatively low, which suggests that it can more easily partition into the lipid bilayer, enhancing its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule's structural features, such as its lipophilicity, aromaticity, and rigidity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 18

**SMILES:** CCN(CC)CCNC(=O)C1CCN(CC1)C2=NN3C=C(N=C3S2)C4=CC=C(C=C4)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the 4-fluorophenyl group, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The overall size of the molecule, including the bulky imidazo[2,1-b][1,3,4]thiadiazole ring, may limit its permeability due to steric hindrance. However, the presence of smaller substituents like the diethylamino group can help balance this effect.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar groups like the phenyl ring and the diethylamino group. This suggests that the molecule may have moderate to high permeability, as it can interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as it can more easily diffuse through the lipid bilayer without encountering significant electrostatic barriers.

5. **Rigidity**: The imidazo[2,1-b][1,3,4]thiadiazole ring system contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings present in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The presence of polar groups like the carboxamide and diethylamino groups may reduce the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is advantageous for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

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# 19

**SMILES:** CC1=CC2=C(C=C1)C(=C(N2CC3=CC=C(C=C3)OC)C(=O)O)CNCC4=CC=CO4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a methoxy group on the phenyl ring and the indole core contribute to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of smaller substituents like the methoxyphenyl and furan-2-ylmethyl groups may help balance this effect.

3. **Polarity**: The molecule contains a carboxylic acid group, which introduces polarity and can form hydrogen bonds. This group may reduce permeability due to its hydrophilic nature. However, the overall low polar surface area, as indicated by the lack of multiple polar groups, suggests that the molecule's lipophilicity might dominate.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indole core provides a degree of rigidity, which can facilitate passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The aromatic rings, including the indole and furan moieties, can enhance lipophilicity and may also participate in π-π interactions with the membrane, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups like the carboxylic acid and the furan oxygen may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the molecule has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilic and hydrophilic interactions with the artificial membrane.

Final answer: Low-to-moderate permeability

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# 20

**SMILES:** CC(=O)C1=CC=C(C=C1)N2CCN(CC2)C3=C(C=C(C=C3)NC(=O)C4=CC=C(C=C4)F)C(=O)O

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The given molecule contains several aromatic rings, including a fluorobenzoyl group and a piperazine ring, which contribute to its lipophilic character. The presence of fluorine in the fluorobenzoyl group can enhance lipophilicity due to its electronegativity, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.42 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and a piperazine moiety suggests that the molecule is rigid, which can improve its ability to permeate the membrane.

3. **Polarity**: The molecule has a polar surface area of 12.8 sq. Å², indicating moderate polarity. The presence of a carboxylic acid group contributes to this polarity, but the overall structure is balanced by the lipophilic aromatic rings, suggesting moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and piperazine structure provide a degree of rigidity, which can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The given molecule has a hydration energy of 0.93 kcal/mol, which is relatively low. This suggests that the molecule can easily transition from an aqueous environment to a lipid environment, facilitating permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between hydrophilic and hydrophobic interactions with the artificial membrane.

Final answer: Low-to-moderate permeability

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# 21

**SMILES:** C1CCN(CC1)C2CCN(CC2)C3=C(C=C(C=C3)NC(=O)C4=CC=C(C=C4)Br)C(=O)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The given molecule contains a bromobenzoyl group, which is a halogenated aromatic ring. Halogen atoms like bromine increase lipophilicity, which generally enhances membrane permeability. However, the overall lipophilicity will depend on the balance with other polar groups.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434. This size can limit permeability due to steric hindrance and the difficulty of passing through the lipid bilayer. However, the specific arrangement of functional groups can mitigate this effect.

3. **Polarity**: The molecule has a low polar surface area, which is a result of the aromatic rings and the presence of a carboxylic acid group. The carboxylic acid group can form hydrogen bonds, which may enhance interactions with the membrane, but the overall low polar surface area suggests good permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of piperidine and phenyl rings contributes to the rigidity of the molecule. Rigidity can improve permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings in the structure can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of a carboxylic acid group suggests that the molecule may have moderate hydration energy, which can influence its solubility and permeability. Lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

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# 22

**SMILES:** CC1=C(C=C(C=C1)C2=NN3C(=NN=C3C4=CC=CC=C42)C)S(=O)(=O)NC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a quinazoline derivative, which is a class of compounds known for their diverse biological activities. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the quinazoline core and the methyl group on the triazoloquinazoline moiety contribute to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings, including a triazole and quinazoline system. While these rings contribute to the rigidity of the molecule, they also increase the molecular weight. The balance between rigidity and size suggests that the molecule might have moderate permeability, as larger and more rigid molecules can have difficulty permeating membranes.

3. **Polarity**: The sulfonamide group introduces some degree of polarity to the molecule. However, the overall structure is dominated by the lipophilic aromatic rings, which likely outweigh the polar contributions. This suggests that the molecule may have moderate polarity, which could impact its permeability.

4. **Charge**: The given molecule is neutral, which is typical for many pharmacologically active compounds. This neutrality allows the molecule to interact favorably with the lipid bilayer of the artificial membrane, potentially leading to moderate to high permeability.

5. **Rigidity**: The presence of multiple aromatic rings and the triazole moiety contributes to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the quinazoline and triazole systems can engage in π-π interactions with the lipid bilayer, which may enhance permeability. However, the presence of these rings also contributes to the overall lipophilicity, which can further support permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a moderate hydration energy. This can influence its ability to permeate the membrane, as molecules with lower hydration energy are generally more permeable.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, as indicated by its structural features. This balance is crucial for permeability, as it allows the molecule to interact favorably with the membrane while maintaining solubility in the aqueous environment.

Overall, considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay.

Final answer: Moderate permeability.

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# 23

**SMILES:** C1=C(OC(=C1)[N+](=O)[O-])C=NNC(=O)C(=O)N

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA). 

Firstly, the presence of a nitrofuran moiety contributes to the molecule's lipophilicity. The nitro group is a strong electron-withdrawing group, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability. However, the nitro group also introduces polarity, which can affect the overall balance between hydrophilicity and lipophilicity.

The furan ring, being an aromatic heterocycle, contributes to the molecule's rigidity and planarity. This rigidity can facilitate the passage of the molecule through the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer. The aromatic nature of the furan ring can also enhance lipophilicity, which is generally favorable for membrane permeability.

The molecule also contains an amide linkage, which can introduce some degree of polarity due to the presence of the carbonyl group. However, amides are generally less polar than other functional groups, such as alcohols or carboxylic acids, and can contribute to the overall lipophilicity of the molecule.

The presence of a hydrazide group introduces additional polarity due to the nitrogen and oxygen atoms, which can form hydrogen bonds. However, the overall effect on permeability will depend on the balance between the polar and non-polar regions of the molecule.

In summary, the given molecule's structural features suggest that it has a balanced lipophilicity and polarity, which may result in moderate permeability through the artificial membrane. The nitrofuran moiety and aromatic furan ring contribute to its lipophilicity, while the amide and hydrazide groups introduce some polarity. These factors collectively influence its permeability in the PAMPA assay.

Final answer: Low-to-moderate permeability

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# 24

**SMILES:** C1COCCN1C2=CC(=O)C3=C(O2)C4=CC=CC=C4C=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound that includes a naphtho[2,1-b]chromenone core structure, which is a fused aromatic system, and a morpholine ring, which is a heterocyclic amine. 

Analyzing the properties:

1. **Lipophilicity**: The aromatic naphtho[2,1-b]chromenone core contributes to the lipophilic nature of the molecule, enhancing its ability to interact with the lipid components of the artificial membrane. This suggests a high permeability.

2. **Molecular Size and Weight**: The presence of a large, rigid aromatic system may limit the permeability due to steric hindrance, but the overall size is balanced by the smaller morpholine ring, which may still allow for sufficient permeability.

3. **Polarity**: The morpholine ring introduces some polarity due to its nitrogen and oxygen atoms, which can form hydrogen bonds. However, the overall structure is dominated by the lipophilic aromatic system, suggesting that the molecule's polarity is not a significant barrier to permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic system provides a rigid structure, which can facilitate passage through the membrane by allowing the molecule to maintain a consistent orientation and conformation.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar functional groups, such as the morpholine ring, may reduce the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance between hydrophilic and hydrophobic regions in the molecule suggests it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule's structural features, such as its lipophilic aromatic core, balanced polarity, and neutral charge, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

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# 25

**SMILES:** CN1C(=NN=N1)SC2=NC=NC3=C2C=CS3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a thienopyrimidine derivative with a specific substitution pattern. Let's analyze its structural features to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the thienopyrimidine core, which is a heterocyclic aromatic compound, contributes to the lipophilicity of the molecule. Additionally, the tetrazole ring, which is a nitrogen-rich heterocycle, can also enhance lipophilicity due to its aromatic nature. The thienopyrimidine and tetrazole rings are likely to increase the overall lipophilicity of the molecule, suggesting a potential for high permeability.

2. **Molecular Size and Weight**: The given molecule is relatively small, with a molecular weight that is not excessively high. This size allows it to traverse the artificial membrane more easily compared to larger, more complex molecules.

3. **Polarity**: The molecule has a low polar surface area due to the presence of multiple aromatic rings and the tetrazole group, which are non-polar. This low polarity suggests that the molecule can interact favorably with the lipid components of the artificial membrane, enhancing its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings in the thienopyrimidine and tetrazole contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The aromatic nature of the thienopyrimidine and tetrazole rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of the tetrazole ring, which is known for its ability to form stable interactions with water, may lower the hydration energy of the molecule. This can enhance its ability to permeate the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 26

**SMILES:** C1=CC=C(C=C1)NC(=O)CCCCCCC(=O)NO

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of an amide group, which is a common functional group in many bioactive molecules, suggests that the molecule has a certain degree of polarity. However, the amide group is relatively polar, and in this case, it is flanked by a long hydrocarbon chain, which contributes to the overall lipophilicity of the molecule. This balance between polar and non-polar regions can enhance the molecule's ability to interact with the lipid bilayer of the artificial membrane, potentially leading to moderate permeability.

Additionally, the hydroxamic acid moiety introduces a hydroxyl group attached to a nitrogen atom, which can form hydrogen bonds. This feature can increase the molecule's solubility in water and may also contribute to interactions with the membrane, potentially affecting permeability.

The aromatic phenyl group attached to the amide nitrogen adds to the lipophilicity and may enhance the molecule's ability to penetrate the lipid bilayer due to its planar structure, which can facilitate interactions with the hydrophobic regions of the membrane.

Overall, the given molecule's structure suggests a balance between hydrophilic and hydrophobic properties, with a moderate degree of rigidity and aromaticity. These characteristics likely contribute to a moderate permeability in the PAMPA assay, as the molecule can interact with both the aqueous and lipid phases of the membrane.

Final answer: Low-to-moderate permeability.

------
# 27

**SMILES:** CN(C)C1=CC=C(C=C1)C2=C(C(=O)NC=C2)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of pyridinone, characterized by a pyridinone core structure with an amino group and a dimethylamino-substituted phenyl group. Let's analyze its properties to predict its permeability in the PAMPA assay:

1. **Lipophilicity**: The presence of the dimethylamino group on the phenyl ring increases the lipophilicity of the molecule. This group is electron-donating, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing permeability.

2. **Molecular Size and Weight**: The given molecule is relatively small, which generally contributes to higher permeability. The pyridinone core and the attached phenyl group are not excessively large, suggesting that the molecule can pass through the artificial membrane with relative ease.

3. **Polarity**: The amino group and the pyridinone moiety introduce some degree of polarity. However, the overall structure is balanced by the lipophilic dimethylamino group, which may reduce the overall polarity. This balance can favor permeability as it allows the molecule to interact with both the aqueous and lipid phases.

4. **Charge**: The given molecule is neutral, which is favorable for permeability. Charged molecules often have reduced permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The pyridinone core provides a degree of rigidity, which can facilitate passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The phenyl group contributes to the aromatic character of the molecule, which can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The presence of polar groups like the amino and pyridinone moieties may lead to moderate hydration energy. However, the overall structure is balanced, which might not significantly hinder permeability.

8. **Membrane Affinity**: The given molecule appears to have a balanced affinity for both the aqueous and lipid phases, which is typically desirable for good permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and favorable structural characteristics.

Final answer: High permeability

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# 28

**SMILES:** COC1=C(C=C(C=C1)C2=CSC(=N2)N3CCC(CC3)C(=O)N)OC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring, which is a five-membered ring containing both sulfur and nitrogen, contributes to the molecule's aromaticity and potential for electronic interactions. This can enhance the molecule's ability to interact with the lipid bilayer, potentially increasing its permeability.

The dimethoxyphenyl group, which is a phenyl ring substituted with two methoxy groups, increases the lipophilicity of the molecule. Methoxy groups are electron-donating, which can enhance the molecule's ability to penetrate lipid membranes by increasing its hydrophobic character.

The overall molecular structure, with its combination of aromatic rings, heteroatoms, and functional groups, suggests that the given molecule has a balanced lipophilicity and polarity. This balance is likely to result in moderate permeability through the artificial membrane, as the molecule can interact with both the hydrophobic and hydrophilic components of the membrane.

Therefore, the given molecule is expected to have a low-to-moderate permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: Low-to-moderate permeability

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# 29

**SMILES:** COC1=CC(=CC(=C1OC)OC)C2=CSC(=N2)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring indicates a heterocyclic aromatic component, which can contribute to the molecule's lipophilicity and ability to interact with the lipid bilayer. The thiazole ring is known for its electron-rich nature, which can enhance interactions with the membrane.

The trimethoxyphenyl group is a bulky, lipophilic moiety that increases the overall hydrophobic character of the molecule. This group can enhance the molecule's ability to traverse the lipid bilayer due to increased lipophilicity.

The piperidine ring is a saturated, nitrogen-containing heterocycle that can contribute to the molecule's basicity and potential for forming hydrogen bonds. This can affect the molecule's solubility and permeability, with the potential to interact with the polar head groups of the lipid bilayer.

Overall, the given molecule's combination of aromatic and heterocyclic components, along with its lipophilic and polar functional groups, suggests that it would exhibit high permeability in the PAMPA assay. The balance of hydrophobic and hydrophilic properties, along with the structural rigidity and flexibility, supports its ability to diffuse through the artificial membrane.

Final answer: High permeability

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# 30

**SMILES:** CC(=O)NC1CCN(CC1)C2=NC(=CS2)C3=CC=C(C=C3)Br

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a bromophenyl group contributes to the lipophilic nature of the molecule. Bromine is a halogen, and its presence can enhance lipophilicity due to its electron-withdrawing properties, which can increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The molecule contains a thiazole ring and a piperidine ring, which are relatively small compared to larger macrocyclic or polycyclic structures. The overall molecular size and weight are moderate, which suggests that the molecule is not too large to permeate the membrane but may still face some limitations due to steric hindrance.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and the thiazole moiety, which are relatively non-polar. Additionally, the acetamide group contributes to the polarity, but the overall structure is balanced, suggesting moderate polarity. This balance can enhance permeability by allowing the molecule to interact with both the aqueous and lipid phases.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid bilayers due to their inability to dissolve in the hydrophobic environment.

5. **Rigidity**: The thiazole and piperidine rings introduce some rigidity to the molecule. Rigidity can help the molecule maintain a conformation that is favorable for permeation, potentially allowing it to fit into the lipid bilayer more effectively.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl and thiazole rings, can enhance lipophilicity and facilitate interactions with the lipid bilayer through π-π interactions. This can contribute to the molecule's ability to permeate the membrane.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which is beneficial for permeability as it indicates that the molecule can easily transition from an aqueous environment to a lipid environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable membrane affinity, allowing it to interact with both the aqueous and lipid phases of the artificial membrane.

Overall, the given molecule exhibits a combination of lipophilic, moderate polar, and rigid characteristics that favor its permeability in the PAMPA assay. These structural features suggest that the molecule would have high permeability through the artificial membrane.

Final answer: High permeability

------
# 31

**SMILES:** CC1=NC(=CC=C1)C2=C(N=C(N2)C(C)(C)C)C3=CC4=NC=CN=C4C=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinoxaline derivative, which is a class of compounds known for their diverse biological activities. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of a pyridine and a methylpyridine group contributes to the lipophilic nature of the molecule. These aromatic nitrogen-containing rings can enhance lipophilicity, which generally increases permeability up to a certain threshold.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a tert-butyl group. While these features can increase molecular weight, the overall size and weight are balanced by the presence of smaller functional groups, which may still allow for moderate permeability.

3. **Polarity**: The pyridine and quinoxaline rings introduce some degree of polarity due to their nitrogen atoms. However, the overall polar surface area is relatively low, and the presence of hydrogen bond donors and acceptors is limited, which can contribute to higher permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and influence interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The tert-butyl group and aromatic rings may lower the hydration energy of the molecule, making it easier for the molecule to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests it has a favorable membrane affinity, which can enhance its permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable structural properties for membrane interaction.

Final answer: High permeability

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# 32

**SMILES:** C1=CC(=CC(=C1)N2C=CC=C2/C=C/3\C(=O)N(C(=O)N3)C4=CC(=CC=C4)Cl)C(=O)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chlorophenyl group and an imidazolidine-dione moiety suggests that the molecule has significant lipophilic character. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.3 g/mol. While size can be a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help to maintain some degree of rigidity and planarity, which can aid in permeation.

3. **Polarity**: The molecule contains a pyrrole ring and an imidazolidine-dione group, which contribute to its polar character. However, the overall polar surface area is balanced by the lipophilic aromatic and chlorinated groups, suggesting moderate polarity. This balance can favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The presence of aromatic rings and a conjugated system in the molecule contributes to its rigidity. This rigidity can enhance its ability to permeate the membrane by maintaining a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The pyrrole and chlorophenyl groups contribute to the aromatic character of the molecule, which can influence its interaction with the membrane. Aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure, with its aromatic and heterocyclic components, suggests a lower hydration energy. This property can facilitate membrane permeation by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a moderate affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, rigidity, and favorable membrane interactions.

Final answer: High permeability

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# 33

**SMILES:** CC1(CCC(=C(C1)CN2CCN(CC2)C3=CC=C(C=C3)C(=O)NS(=O)(=O)C4=CC(=C(C=C4)N[C@H](CCN5CCOCC5)CSC6=CC=CC=C6)S(=O)(=O)C(F)(F)F)C7=CC=C(C=C7)Cl)C

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl and chlorophenyl groups, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The molecule is relatively large, as indicated by its molecular weight of 1051. This size can limit permeability due to steric hindrance and the difficulty in passing through the artificial membrane. However, the specific arrangement of functional groups and the overall shape of the molecule can still allow for sufficient permeability.

3. **Polarity**: The molecule contains several polar groups, including the sulfonamide, ether, and amide linkages. These groups can form hydrogen bonds, which may reduce overall lipophilicity and limit permeability. However, the balance between lipophilic and polar components will determine the overall permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings and the piperidine moiety contribute to the rigidity of the molecule. This rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can affect its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests that it may have a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity. However, the large size and specific functional groups may impose some limitations on its permeability.

Final answer: High permeability

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# 34

**SMILES:** CCCCCCCCC1=CC=C(C=C1)CCC(CO)(CO)N

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to the permeability characteristics mentioned earlier.

1. **Lipophilicity**: The given molecule contains a long octyl chain attached to a phenyl group. This hydrophobic chain increases the lipophilicity of the molecule, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight due to its complex structure, which includes multiple functional groups. While size can be a limiting factor for permeability, the presence of a long hydrophobic chain may offset this to some extent by increasing lipophilicity.

3. **Polarity**: The molecule contains two hydroxyl groups and an amino group, which contribute to its polarity. However, the overall polarity is balanced by the long hydrophobic chain, suggesting moderate polarity. The presence of these polar groups can form hydrogen bonds, which may aid in interactions with the aqueous environment, but they also introduce some steric hindrance.

4. **Charge**: The molecule is neutral, as it does not contain any charged functional groups. This neutrality is favorable for permeability, as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic phenyl ring in the structure contributes to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The phenyl group can also influence lipophilicity and membrane interactions. Aromatic rings can participate in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of hydroxyl and amino groups suggests that the molecule may have moderate hydration energy. This can affect its solubility and permeability, with lower hydration energy generally improving membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural features that favor interaction with lipid membranes.

Final answer: High permeability

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# 35

**SMILES:** CN(C)[C@@H]1CCN(C1)C2=CC=CC(=C2)NC3=NN4C(=O)C5=CC=CC=C5N=C4S3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the dimethylamino phenyl group and the quinazolinone moiety, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule contains a pyrrolidine ring and a quinazolinone core, which contribute to its overall size and molecular weight. While these features can limit permeability due to steric hindrance, the balance of lipophilicity and size suggests moderate permeability.

3. **Polarity**: The dimethylamino group introduces some polarity, but the overall structure is dominated by aromatic and heterocyclic components, which are less polar. This suggests that the molecule has a relatively low polar surface area, favoring higher permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to traverse lipid membranes.

5. **Rigidity**: The quinazolinone and pyrrolidine rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of heteroatoms like nitrogen and oxygen in the quinazolinone and pyrrolidine rings may lead to moderate hydration energy, which can influence membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, moderate size, balanced polarity, and favorable interactions with the artificial membrane.

Final answer: High permeability

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# 36

**SMILES:** CCNC(=O)C1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NCC4CCCO4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key functional groups and structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the quinazoline and furan moieties, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The overall size of the molecule, including the oxolan-2-ylmethylamino group and the furan-2-carboxamide moiety, suggests a moderate molecular weight. While larger molecules can have reduced permeability, the specific arrangement of these groups may still allow for sufficient permeation.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and the absence of highly polar functional groups. This contributes to its ability to interact with the hydrophobic environment of the lipid bilayer, enhancing permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The quinazoline core provides a rigid structure, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings in the quinazoline and furan moieties can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to transition from an aqueous to a lipid environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a favorable membrane affinity, which is essential for high permeability in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, and structural rigidity, alongside its ability to interact with the lipid bilayer effectively.

Final answer: High permeability

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# 37

**SMILES:** CC1=C(C(N=C(N1)NC2=NC3=CC=CC=C3O2)C4=NN(C=C4Cl)C)C(=O)NC5=NN=CS5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including the benzoxazole and pyrazole moieties, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of multiple aromatic and heterocyclic rings may allow for some degree of flexibility, which can mitigate the negative effects of size.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to polarity. However, the overall structure is dominated by aromatic and heterocyclic rings, which are generally non-polar. The low polar surface area and the presence of hydrogen bond donors and acceptors suggest that the molecule may have moderate polarity, which could influence its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to a rigid structure, which can enhance the ability of the molecule to permeate the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings, particularly the benzoxazole and pyrazole, can interact with the lipid bilayer, potentially enhancing permeability through hydrophobic interactions.

7. **Hydration Energy**: The presence of multiple nitrogen atoms and heterocycles suggests that the molecule may have a lower hydration energy, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it may have a favorable affinity for both the aqueous phase and the lipid bilayer, which is advantageous for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, aromaticity, and balanced polarity.

Final answer: High permeability

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# 38

**SMILES:** CC1=C(C=CC(=C1)SCC2=C(N=C(S2)C3=CC=C(C=C3)C(F)(F)F)C)OCC(=O)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA). Let's analyze these features:

1. **Lipophilicity**: The presence of trifluoromethyl groups and aromatic rings in the structure suggests a high degree of lipophilicity. These groups increase the molecule's hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434.5 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and a thiazole moiety may contribute to a more rigid structure, potentially offsetting the negative impact of size.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of non-polar groups like the trifluoromethyl and phenyl rings. This low polarity is likely to enhance permeability, as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The thiazole ring and aromatic systems contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less likely to form strong interactions with water, which can aid in permeating the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

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# 39

**SMILES:** CC1=CC(=NC(=C1)NC(=S)N2CCN(CC2)C3=CC=NC=C3)C

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the dimethylpyridine moiety contributes to the lipophilic character of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane, as lipophilic compounds tend to have higher permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large, which may limit its permeability due to steric hindrance. However, the presence of the piperazine ring can help to balance this by providing some flexibility and reducing steric bulk.

3. **Polarity**: The pyridine rings and the carbothioamide group introduce some degree of polarity to the molecule. While this can reduce permeability, the overall balance of lipophilic and polar groups suggests moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The aromatic pyridine rings contribute to the rigidity of the molecule. This rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The pyridine rings also contribute to the aromatic character of the molecule, which can influence lipophilicity and interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of nitrogen atoms in the pyridine and piperazine rings can lead to moderate hydration energy, which may aid in membrane permeation by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and polarity, and having a stable conformation that allows it to interact effectively with the artificial membrane.

Final answer: Low-to-moderate permeability

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# 40

**SMILES:** CC1=CC(=NC(=C1)NC(=S)N2CCN(CC2)C3=C(C=C(C=C3)F)F)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperazine derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the dimethylpyridine and difluorophenyl groups contributes to the lipophilic nature of the molecule. These groups increase the overall hydrophobic character, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The piperazine ring and the attached functional groups contribute to a moderate molecular size. While larger molecules can have issues with permeability, the balance of hydrophobic and hydrophilic groups in the given molecule suggests it may still have sufficient permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar groups like the difluorophenyl and dimethylpyridine. Additionally, the carbothioamide group introduces some polarity, but the overall effect is a balance that may favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings in the difluorophenyl and pyridine groups contribute to a degree of rigidity, which can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of fluorine atoms and aromatic groups can lower the hydration energy, making it easier for the molecule to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the given molecule has a favorable membrane affinity, which is conducive to higher permeability.

Overall, the given molecule exhibits a combination of lipophilic, aromatic, and rigid structural features that suggest it would have high permeability in the PAMPA assay.

Final answer: High permeability

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# 41

**SMILES:** CC1=CC(=NO1)NS(=O)(=O)C2=CC=C(C=C2)C(=O)NCC3=CC(=C(C=C3)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features.

1. **Lipophilicity**: The presence of the dichlorophenyl group contributes to the lipophilic nature of the molecule. Chlorine atoms increase the lipophilicity due to their electron-withdrawing properties, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively complex, with multiple aromatic rings and functional groups. While the aromatic rings can increase the molecular weight, the overall size and weight are balanced by the smaller sulfonamide and isoxazole groups, which may still allow for sufficient permeability.

3. **Polarity**: The sulfonamide group introduces some polarity, but the overall polar surface area is relatively low due to the presence of the aromatic rings and the dichlorophenyl group. This suggests that the molecule may have moderate polarity, which can influence its permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings and the isoxazole moiety contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the sulfonamide group and the isoxazole ring may lower the hydration energy, facilitating the molecule's passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and structural rigidity.

Final answer: High permeability

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# 42

**SMILES:** CC1=CC(=NC=C1)NC(=S)N2CCN(CC2)C3=C(C=C(C=C3)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the dichlorophenyl group contributes to the lipophilic nature of the molecule. Chlorine atoms increase the lipophilicity due to their electron-withdrawing properties, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings and the piperazine moiety can help to balance this by providing rigidity and planarity, which can facilitate passage through the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and the absence of multiple polar functional groups. This low polarity can enhance its permeability as it allows the molecule to interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings and the piperazine ring contribute to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The presence of aromatic rings can also influence the molecule's lipophilicity and its ability to interact with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can facilitate its permeation through the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability in PAMPA assays.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that suggest it would have high permeability in the PAMPA assay.

Final answer: High permeability

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# 43

**SMILES:** CC1=CC(=NO1)NS(=O)(=O)C2=CC=C(C=C2)NC(=O)CC3=CC(=C(C=C3)F)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups, contributes to the lipophilicity of the molecule. The chloro and fluoro substituents on the phenyl ring further enhance lipophilicity due to their electron-withdrawing nature, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a sulfonamide group. While the sulfonamide moiety is polar, the overall size and complexity may limit its permeability compared to smaller molecules.

3. **Polarity**: The sulfonamide group introduces some polarity, which can hinder permeability. However, the overall polar surface area is balanced by the lipophilic aromatic rings, which may still allow for sufficient permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without being repelled by a charge.

5. **Rigidity**: The presence of aromatic rings and the oxazole moiety contribute to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by maintaining a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide, may lead to moderate hydration energy, which can affect membrane permeation. However, the overall balance of lipophilic and polar groups suggests that the hydration energy is not a significant barrier.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is indicative of good permeability in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, neutral charge, and structural rigidity.

Final answer: High permeability

------
# 44

**SMILES:** C1CCC2=C(C1)N=C3CCCCC3=N2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of phenazine, specifically a hexahydrophenazine. This structure indicates that the phenazine core has been partially hydrogenated, resulting in a more saturated and flexible molecule compared to its fully aromatic counterpart.

1. **Lipophilicity**: The partial hydrogenation of the phenazine core increases the saturation of the molecule, which can enhance its lipophilicity. This increased lipophilicity generally correlates with higher permeability through lipid membranes.

2. **Molecular Size and Weight**: The hexahydrophenazine structure suggests a relatively small molecular size and weight compared to fully aromatic phenazines. This smaller size can facilitate diffusion through the artificial membrane, contributing to higher permeability.

3. **Polarity**: The presence of nitrogen atoms in the heterocyclic structure can introduce some polarity, but the overall saturation of the rings reduces the polar surface area. This reduction in polarity can enhance the molecule's ability to permeate the membrane.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The partial hydrogenation results in a less rigid structure compared to fully aromatic phenazines. This increased flexibility can improve the molecule's ability to adapt and permeate the membrane.

6. **Aromaticity**: The aromatic nature of the phenazine core is reduced in the given molecule, which can decrease its interaction with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The reduced aromaticity and increased saturation suggest lower hydration energy, which can facilitate membrane permeation as the molecule requires less energy to transition from an aqueous to a lipid environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests it has a favorable affinity for both the aqueous and lipid phases, enhancing its permeability through the artificial membrane.

Overall, the structural features of the given molecule, such as partial hydrogenation, reduced aromaticity, and increased lipophilicity, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay.

Final answer: High permeability

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# 45

**SMILES:** COC1C(CC2CN3CCC4=C(C3CC2C1CO)NC5=C4C=CC(=C5)OC)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a yohimban alkaloid, which is a class of compounds known for their complex polycyclic structures and biological activity. The yohimban framework is characterized by a multi-ring system that includes both aromatic and non-aromatic rings, contributing to its structural rigidity and lipophilicity.

The presence of methoxy groups in the given molecule increases its lipophilicity, which generally enhances membrane permeability. These groups can also influence the molecule's ability to interact with the lipid bilayer, potentially improving its permeability.

The hydroxyl groups present in the structure can form hydrogen bonds, which may affect the molecule's solubility and permeability. However, in the context of PAMPA, the balance between hydrophilic and lipophilic properties is crucial. The hydroxyl groups may contribute to moderate permeability by providing sites for hydrogen bonding with the membrane or aqueous environment.

The overall structure, with its combination of aromatic and non-aromatic rings, suggests a balance between rigidity and flexibility, which can facilitate membrane permeation. The yohimban scaffold is known for its ability to interact with biological membranes, which aligns with the molecule's potential for moderate to high permeability in the PAMPA assay.

Therefore, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 46

**SMILES:** CN1C2=C(C(=O)N(C1=O)C)NC(=O)N2

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a derivative of xanthine, which is a purine compound. It features a xanthine core with additional methyl groups attached to the nitrogen atoms. This structural modification can influence its physicochemical properties, such as lipophilicity and polarity.

The presence of the xanthine core suggests that the given molecule has a relatively planar and rigid structure, which can facilitate its interaction with the lipid bilayer of the artificial membrane. The methyl groups increase the lipophilicity of the molecule, enhancing its ability to permeate through the hydrophobic regions of the membrane.

Additionally, the molecule's low polar surface area and the absence of significant hydrogen bond donors or acceptors contribute to its permeability. The lack of polar functional groups means the molecule has limited interactions with the aqueous environment, allowing it to focus on permeating the lipid bilayer.

Overall, the given molecule's structural features, including its lipophilicity, rigidity, and lack of polar groups, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 47

**SMILES:** C1CNCCC1NC2=CC=CC(=N2)C3=CN=C4N3C=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a chloro group and an imidazo[1,2-a]pyridine moiety suggests that the molecule has a significant degree of lipophilicity. This is because halogen atoms like chlorine increase lipophilicity, which generally enhances membrane permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, as indicated by its molecular weight of 336.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may contribute to a more rigid structure, potentially aiding in permeability despite the size.

3. **Polarity**: The molecule has a low polar surface area, which is a result of the aromatic and heterocyclic rings. This low polarity, combined with the presence of a piperidine ring, suggests that the molecule is less likely to form strong interactions with water, enhancing its ability to permeate the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The imidazo[1,2-a]pyridine and pyridine rings contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for the molecule to adopt conformations that fit through the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the pyridine and imidazo[1,2-a]pyridine rings can enhance lipophilicity and influence interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to be tightly bound to water molecules, which can enhance its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, rigidity, and balanced polarity.

Final answer: High permeability

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# 48

**SMILES:** CCOC1=CC=CC=C1C(=O)NC2=C(C=NC=C2)C(=O)NC3=CC(=CC=C3)S(=O)(=O)C(F)(F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a benzamide derivative, which suggests it has a planar aromatic structure that can interact with lipid membranes. The presence of the benzamide group indicates potential hydrogen bonding capabilities, which can influence its interaction with the artificial membrane.

The molecule contains an ethylsulfonyl group attached to a phenyl ring. This group is polar and can increase the molecule's solubility in water, potentially affecting its permeability. However, the sulfonyl group can also enhance lipophilicity due to its ability to stabilize the molecule's interaction with the lipid bilayer.

The pyridine ring in the structure contributes to the molecule's aromaticity and can enhance its ability to interact with the lipid membrane through π-π interactions. This can increase the molecule's permeability.

The molecule's overall structure, with its combination of aromatic rings and polar functional groups, suggests a balance between hydrophilic and lipophilic properties. This balance can facilitate its passage through the artificial membrane, indicating that the given molecule likely exhibits high permeability in the PAMPA assay.

Final answer: High permeability

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# 49

**SMILES:** C1=CC=C(C=C1)COC2=CC(=CC=C2)SC3=CC(=C(C=C3)CCC(CO)(CO)N)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and phenylsulfanyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.45 g/mol. While size is a critical factor in permeability, the presence of multiple functional groups and aromatic rings may allow for specific interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule contains amino, hydroxyl, and sulfanyl groups, which contribute to its polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can enhance membrane permeability by allowing the molecule to interact with both hydrophilic and hydrophobic environments.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their inability to interact favorably with the hydrophobic nature of the membrane.

5. **Rigidity**: The aromatic rings and the sulfanyl linkage contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The presence of multiple aromatic rings can further enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The molecule's structure, with both hydrophilic and hydrophobic components, suggests a moderate hydration energy. This balance can aid in permeability by allowing the molecule to interact with the aqueous environment while also engaging with the lipid membrane.

8. **Membrane Affinity**: The combination of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and structural rigidity.

Final answer: High permeability

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# 50

**SMILES:** C1CCC(C1)C2=C(C=CC(=C2)C3=CNC4=C3C=C(C=N4)C5=CC=CC=C5)C(=O)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to the permeability characteristics mentioned earlier.

1. **Lipophilicity**: The given molecule contains a cyclopentyl group and a pyrrolo[2,3-b]pyridine moiety, which contribute to its overall lipophilicity. These hydrophobic groups suggest that the molecule may have a high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The presence of a phenyl group and a pyridine ring indicates a relatively large molecular structure. While size can be a limiting factor for permeability, the aromatic nature of these rings may enhance lipophilicity and facilitate membrane interaction.

3. **Polarity**: The molecule has a carboxylic acid group, which introduces some polarity. However, the overall structure is dominated by hydrophobic aromatic rings, suggesting that the polar surface area is not high enough to significantly impede permeability.

4. **Charge**: The molecule is neutral, as it is not described as having any charged groups. This neutrality is favorable for permeability, as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic rings, including the phenyl and pyridine groups, can influence the molecule's lipophilicity and its ability to interact with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The aromatic and hydrophobic nature of the molecule suggests that it may have a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases of the membrane.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and structural rigidity, which facilitate its interaction with the artificial membrane.

Final answer: High permeability

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# 51

**SMILES:** CC[C@@H](C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a fluorinated quinazoline derivative with several structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of a fluorine atom on the quinazoline ring increases the lipophilicity of the molecule. Fluorine is highly electronegative, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively complex, with multiple rings and heteroatoms. While the quinazoline core is relatively planar, the additional substituents, such as the fluoro group and the purine moiety, may increase the molecular size and weight. This could lead to moderate permeability, as larger molecules may have reduced diffusion rates through the membrane.

3. **Polarity**: The purine moiety contributes to the molecule's overall polarity, as it contains nitrogen atoms capable of forming hydrogen bonds. However, the presence of the fluoroquinazoline moiety and the aromatic rings may balance this by increasing lipophilicity, potentially resulting in moderate permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The quinazoline and purine rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The aromatic rings in the quinazoline and purine structures can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups, such as the purine nitrogen atoms, may lead to moderate hydration energy, which can affect the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, considering these structural characteristics, the given molecule is likely to exhibit moderate permeability in the PAMPA assay.

Final answer: Low-to-moderate permeability

------
# 52

**SMILES:** CC1=C(C=C(C=C1)C(=O)N)NC2=NC=CC(=N2)C3=CN(C4=C3C=CN=C4)C(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrrolo[2,3-b]pyridine and pyridine moieties, contributes to the lipophilic character of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a limiting factor for permeability, the presence of multiple aromatic rings and heterocycles may allow for favorable interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of a relatively non-polar compound. This low polarity can enhance its ability to traverse the lipid bilayer, contributing to high permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles introduces rigidity to the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the membrane, potentially enhancing its permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less likely to form strong interactions with water, which can facilitate its passage through the hydrophobic environment of the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Overall, the given molecule exhibits several structural features that suggest high permeability in the PAMPA assay, including its lipophilicity, aromaticity, rigidity, and balanced polarity.

Final answer: High permeability

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# 53

**SMILES:** CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the indole and phenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of multiple aromatic rings and a bulky structure may still allow for sufficient permeation, but it might be balanced by other factors.

3. **Polarity**: The molecule contains several polar groups, including hydroxyl and carbonyl groups. However, the overall polar surface area is relatively low due to the dominance of aromatic and hydrophobic moieties. This suggests that the molecule may have moderate polarity, which can influence its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a relatively planar indole structure suggests a degree of rigidity. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation.

6. **Aromaticity**: The aromatic systems in the molecule contribute to its lipophilicity and may also participate in π-π interactions with the membrane, enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous phase.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural features that facilitate membrane interaction.

Final answer: High permeability

------
# 54

**SMILES:** COC1=C(N=C(O1)C2=CC=CC3=CC=CC=C32)C(=O)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of a naphthalene moiety contributes to the lipophilicity of the molecule. Naphthalene rings are aromatic and hydrophobic, which generally enhances the molecule's ability to interact with the lipid components of the artificial membrane, thus increasing permeability.

Secondly, the oxazole ring in the structure is a heterocyclic compound that can contribute to the molecule's overall stability and rigidity. This rigidity can facilitate the passage of the molecule through the membrane by reducing the likelihood of conformational changes that might hinder permeation.

The methoxy group attached to the oxazole ring introduces a slight increase in polarity, but its presence is relatively minor compared to the overall hydrophobic character of the molecule. This group can also influence the molecule's solubility and interaction with the membrane, potentially enhancing permeability.

The carboxylic acid functional group is polar and can form hydrogen bonds, which might affect the molecule's interaction with the membrane. However, in the context of PAMPA, the carboxylic acid group is likely to be deprotonated, reducing its polarity and enhancing the molecule's lipophilicity, thus improving permeability.

Overall, the given molecule's combination of aromaticity, rigidity, and moderate polarity suggests that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 55

**SMILES:** CCNC(=O)C[C@H]1C2=NN=C(N2C3=C(C=C(C=C3)OC)C(=N1)C4=CC=C(C=C4)Cl)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a member of the triazolobenzodiazepine class, which is known for its central nervous system activity. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features:

1. **Lipophilicity**: The presence of a chlorophenyl group and a methoxy group suggests that the molecule is relatively lipophilic. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, contributing to higher permeability.

2. **Molecular Size and Weight**: The triazolobenzodiazepine core is a relatively large and complex structure, which may limit the molecule's permeability due to steric hindrance. However, the presence of a methoxy group and a methyl group can reduce the overall molecular weight and improve permeability.

3. **Polarity**: The molecule contains a polar acetamide group, which can form hydrogen bonds. While this may contribute to some degree of polarity, the overall structure is dominated by lipophilic groups, suggesting that the polar surface area is not high enough to significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The triazolobenzodiazepine core provides a rigid structure, which can facilitate passage through the membrane by reducing the number of conformational changes required.

6. **Aromaticity**: The aromatic rings present in the structure can enhance lipophilicity and may also participate in π-π interactions with the membrane, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule has moderate hydration energy, which can influence its permeability by affecting the energy required to remove water molecules from the surface of the molecule.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a favorable affinity for both the aqueous and lipid phases, which is generally beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, structural rigidity, and moderate polarity.

Final answer: High permeability

------
# 56

**SMILES:** C1=CC=C2C(=C1)C(=NC(=N2)N3C=CN=C3)NC4=CC(=C(C=C4)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinazoline derivative, which is a class of compounds known for their biological activity, often used in pharmaceuticals. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the quinazoline core and the aromatic rings contributes to the lipophilic nature of the molecule. The difluorophenyl group further enhances lipophilicity due to the fluorine atoms, which increase the electron density and hydrophobic character.

2. **Molecular Size and Weight**: The given molecule is relatively small, which is beneficial for permeability. The quinazoline core and the attached aromatic rings contribute to a compact structure, which can facilitate passage through the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic rings and the absence of multiple polar functional groups. The presence of nitrogen atoms in the quinazoline and pyrazole rings can participate in hydrogen bonding, but overall, the molecule is expected to have low polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The quinazoline and pyrazole rings introduce rigidity to the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation during passage.

6. **Aromaticity**: The aromatic rings in the structure can interact with the lipid bilayer through π-π interactions, which can aid in membrane permeation.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it can easily transition from an aqueous environment to a lipid environment, facilitating membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests that it has a favorable membrane affinity, which is essential for high permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, compact structure, and favorable interactions with the lipid bilayer.

Final answer: High permeability

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# 57

**SMILES:** C1=CC=C2C(=C1)C(=NC(=N2)NC3=CC=NC=C3)NC4=CC(=C(C=C4)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinazoline derivative with several functional groups and structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the quinazoline core and the difluorophenyl group contribute to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large due to the quinazoline core and the pyridine rings. While size can be a limiting factor for permeability, the presence of aromatic rings can help in spanning the lipid bilayer, potentially offsetting the negative effects of size.

3. **Polarity**: The pyridine rings introduce nitrogen atoms, which can contribute to the polar surface area. However, the difluorophenyl group and the quinazoline core are predominantly hydrophobic, suggesting that the overall polarity might not significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings in the structure provide rigidity, which can facilitate passage through the membrane by maintaining a consistent conformation.

6. **Aromaticity**: The aromatic nature of the quinazoline and pyridine rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of nitrogen atoms and aromatic rings may lower the hydration energy, aiding in membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and balanced polarity.

Final answer: High permeability

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# 58

**SMILES:** C1=CC(=C(C(=C1)[N+](=O)[O-])O)CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC=CS3

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole rings, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple functional groups and rings. While the sulfonamide group itself is relatively small, the overall molecular size and weight may limit its permeability due to steric hindrance.

3. **Polarity**: The molecule contains polar functional groups, such as the sulfonamide and hydroxy groups. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but could also hinder permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the thiazole moiety contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of aromatic rings can enhance lipophilicity and membrane affinity, which is beneficial for permeability.

7. **Hydration Energy**: The hydroxy group and sulfonamide moiety can interact with water molecules, potentially increasing the hydration energy. However, the overall balance of hydrophilic and hydrophobic regions may still allow for sufficient membrane permeation.

8. **Membrane Affinity**: The given molecule has a balanced distribution of hydrophilic and hydrophobic regions, suggesting it can interact effectively with both the aqueous and lipid phases of the membrane.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between its hydrophilic and hydrophobic characteristics.

Final answer: Low-to-moderate permeability

------
# 59

**SMILES:** C1=CC(=CC=C1NCC2=C(C=C(C=C2)N)O)[S+](=O)(NC3=NC=CS3)[O-]

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings and functional groups, which may increase its molecular weight. However, the presence of aromatic rings and the sulfonamide group can also contribute to a compact structure, potentially mitigating the negative impact of size on permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic rings. The amino groups on the phenyl ring and the thiazole ring can also contribute to hydrogen bonding, which may slightly reduce permeability due to increased polarity.

4. **Charge**: The molecule is neutral, which is typical for many drug candidates, allowing it to traverse lipid membranes more effectively than charged molecules.

5. **Rigidity**: The aromatic rings and the thiazole ring contribute to a rigid structure, which can enhance membrane permeability by reducing the flexibility of the molecule and allowing it to fit more easily into the lipid bilayer.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide and amino groups, may lead to moderate hydration energy, which can affect membrane permeation. However, the overall balance of lipophilic and polar groups suggests that the hydration energy is not excessively high.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, as indicated by its structural features. This balance is often associated with favorable permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate molecular size, and balanced polarity.

Final answer: High permeability

------
# 60

**SMILES:** COC1=CC=CC(=C1N)CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC=CS3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings and functional groups, which may increase its molecular weight. However, the presence of aromatic rings and the sulfonamide group can also contribute to a compact structure, potentially mitigating the negative effects of size on permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by aromatic and hydrophobic components. The presence of a methoxy group and an amino group can also contribute to the polarity, but the overall polar surface area is likely moderate.

4. **Charge**: The molecule is neutral, which is typical for many drug candidates, allowing it to traverse lipid membranes more effectively than charged molecules.

5. **Rigidity**: The aromatic rings and the thiazole ring contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide and amino groups, may lead to moderate hydration energy, which can influence membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate polarity, and balanced structural rigidity.

Final answer: High permeability

------
# 61

**SMILES:** CC1=C(NC(=C1C(=O)C)C)C(=O)NC2=CC=C(C=C2)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of aromatic rings, such as the acetylphenyl group, contributes to the lipophilicity of the molecule. Aromatic rings are known to enhance lipophilicity, which can increase the molecule's ability to permeate lipid membranes.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings and functional groups, which may increase its molecular weight. However, the presence of aromatic rings and the amide linkage can also contribute to a compact structure, potentially mitigating the negative effects of size on permeability.

3. **Polarity**: The amide group introduces some polarity, but the overall structure is dominated by the lipophilic aromatic rings. The balance between these polar and non-polar regions can influence the molecule's ability to interact with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the pyrrole ring contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can facilitate interactions with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of the amide group and aromatic rings suggests that the molecule may have a moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule's structure, with its aromatic rings, amide linkage, and moderate polarity, suggests that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 62

**SMILES:** CC1=C(NC(=C1C(=O)C)C)C(=O)NC2=CC=C(C=C2)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a certain degree of lipophilicity due to the presence of aromatic rings. Aromatic rings can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

The presence of a chlorophenyl group indicates that the molecule has a degree of hydrophobic character, which can further contribute to its permeability. Chlorine atoms can increase lipophilicity and may also influence the electronic properties of the aromatic ring, potentially affecting how the molecule interacts with the membrane.

The pyrrole ring in the structure is a five-membered heterocycle, which can contribute to the rigidity of the molecule. Rigidity can enhance the ability of the molecule to permeate the membrane by reducing the number of conformational changes required during passage through the lipid bilayer.

The carboxamide group in the molecule is a polar functional group, which can form hydrogen bonds with the surrounding environment. However, in this case, the presence of the aromatic ring may reduce the overall polarity of the molecule, allowing it to maintain a balance between hydrophilic and hydrophobic interactions, which is beneficial for membrane permeability.

Overall, the given molecule's combination of aromaticity, hydrophobic groups, and a relatively rigid structure suggests that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 63

**SMILES:** COC1=C(C=C(C=C1)C2CC(=O)NC3=C2SC(=N3)N)OC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is characterized by several structural features that influence its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA). 

Firstly, the presence of a dimethoxyphenyl group indicates a degree of lipophilicity, which generally enhances membrane permeability due to increased hydrophobic interactions with the lipid bilayer. The methoxy groups also contribute to the molecule's overall lipophilicity and can affect its ability to interact with the membrane.

Secondly, the thiazolopyridine core structure suggests a certain degree of rigidity and aromaticity. The aromatic nature of this core can facilitate interactions with the lipid bilayer, potentially enhancing permeability. However, the rigidity of the core may also limit the molecule's flexibility, which could impact its ability to fit into the membrane.

The amino group present in the molecule introduces a polar element, which can form hydrogen bonds with the surrounding environment. While this may increase the molecule's solubility in aqueous environments, it can also hinder permeability through the lipid bilayer due to the polar nature of the interaction.

Additionally, the overall molecular size and weight are relatively moderate, which suggests that while the molecule is not too large to permeate the membrane, it may still face some steric hindrance.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance between its lipophilic and polar characteristics, along with its structural rigidity and aromaticity, suggests that it will have some difficulty permeating the artificial membrane, but not to the extent of being classified as low-to-moderate permeability.

Final answer: Low-to-moderate permeability

------
# 64

**SMILES:** CCN1CCC2=C(C1)SC(=C2C(=O)N)NC(=O)NC3=CC(=C(C=C3)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, specifically the dichlorophenyl group, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic rings and the overall structure may allow for sufficient permeation.

3. **Polarity**: The molecule contains several polar groups, including amide and carbamoyl groups. These groups can form hydrogen bonds, which may facilitate interactions with the aqueous environment and the membrane surface, potentially aiding in permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The thieno[2,3-c]pyridine core provides a degree of rigidity to the molecule. This rigidity can help the molecule maintain a conformation that is favorable for permeation through the membrane.

6. **Aromaticity**: The aromatic rings, including the thieno[2,3-c]pyridine and dichlorophenyl groups, can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a neutral charge, and a rigid structure, which collectively suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 65

**SMILES:** CCOC1=CC=C(C=C1)N2CC(CC2=O)C3=NC(=NO3)C4=CC=CC=N4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and pyridinyl groups, contributes to the lipophilic nature of the molecule. These rings can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The pyridinyl and pyridin groups introduce some degree of polarity to the molecule. However, the presence of these heterocyclic rings can also contribute to the molecule's ability to engage in π-π interactions with the membrane, which can enhance permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The oxadiazol and pyrrolidinone rings introduce rigidity to the molecule. This rigidity can facilitate passage through the membrane by reducing the flexibility of the molecule, which may otherwise hinder its permeability.

6. **Aromaticity**: The aromatic nature of the pyridinyl and pyridin groups can enhance lipophilicity and membrane affinity, which is beneficial for permeability.

7. **Hydration Energy**: The presence of polar groups and heteroatoms like nitrogen and oxygen in the oxadiazol and pyrrolidinone rings may lead to moderate hydration energy. This can affect the molecule's solubility and permeability, potentially allowing it to interact with the membrane without being too water-soluble.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 66

**SMILES:** CC1=CC(=CC(=C1)NC2=NC(=CS2)C3=CC=C(O3)CNC(=O)C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of dimethylphenyl and methyl groups contributes to the lipophilic character of the molecule. These groups increase the hydrophobic interactions with the lipid bilayer, enhancing permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 294.4 g/mol. While size is a factor in permeability, the presence of aromatic and heterocyclic rings can help the molecule maintain a balance between size and permeability.

3. **Polarity**: The molecule has a low polar surface area, which is due to the presence of aromatic rings and the absence of highly polar functional groups. This contributes to its ability to permeate the membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced diffusion through lipid membranes.

5. **Rigidity**: The thiazole and furan rings introduce rigidity to the molecule, which can enhance its ability to permeate the membrane by reducing conformational flexibility.

6. **Aromaticity**: The aromatic rings, including the phenyl and thiazole groups, can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it can easily transition from an aqueous environment to a lipid environment, facilitating membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that contribute to its high permeability in the PAMPA assay.

Final answer: High permeability

------
# 67

**SMILES:** CC1=CSC(=N1)NS(=O)(=O)C2=CC=C(C=C2)NCC3=C(C(=CC=C3)OC)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings and functional groups, which may increase its molecular weight. However, the presence of aromatic rings and a sulfonamide group can also contribute to a compact structure, potentially mitigating the negative effects of size on permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by aromatic and lipophilic components. The presence of a methoxy group and a hydroxyl group also adds to the polarity, but the balance between these polar groups and the lipophilic aromatic rings suggests that the molecule may have a moderate polar surface area.

4. **Charge**: The given molecule is neutral, which is typical for many sulfonamides. This neutrality allows it to interact favorably with the lipid bilayer of the artificial membrane, enhancing its permeability.

5. **Rigidity**: The aromatic rings and the thiazole ring contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups like the hydroxyl and methoxy groups may reduce the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 68

**SMILES:** C1=CC\2=C(C=C1Cl)NC(=O)/C2=C/C3=CC(=C(C(=C3)Cl)O)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of indole, which is a bicyclic structure consisting of a benzene ring fused to a pyrrole ring. This core structure is known for its planar and aromatic nature, which can influence the molecule's interaction with lipid membranes.

The presence of a chlorine atom on the phenyl ring and the indole structure contributes to the molecule's lipophilicity, enhancing its ability to permeate through the lipid bilayer. Chlorine atoms can increase the hydrophobic character of the molecule, which is beneficial for membrane permeability.

The hydroxy group on the phenyl ring introduces a polar element to the molecule, which can form hydrogen bonds with the surrounding environment. However, the overall effect of this group on permeability is likely moderate, as the molecule's lipophilicity is still dominant.

The methylene bridge connecting the phenyl and indole rings introduces a degree of rigidity and planarity, which can facilitate passage through the membrane by allowing the molecule to maintain a consistent orientation and conformation.

Overall, the given molecule's combination of aromaticity, lipophilicity, and moderate polarity suggests that it would exhibit high permeability in the PAMPA assay. The balance of hydrophobic and hydrophilic interactions with the artificial membrane likely supports its diffusion across the lipid layer.

Final answer: High permeability

------
# 69

**SMILES:** C1=CC2=C(C(=C1)Cl)/C(=C\C3=CC(=C(C(=C3)Cl)O)Cl)/C(=O)N2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of chloro groups and a methoxy group contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains polar groups such as hydroxyl and carbonyl groups. However, the presence of multiple chloro groups and a methoxy group can balance this polarity, potentially allowing the molecule to interact favorably with the hydrophobic regions of the membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The presence of aromatic rings, such as the phenyl and indole rings, contributes to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can also influence the lipophilicity and molecular interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can affect its permeability. Lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it may have a favorable affinity for both the aqueous phase and the lipid bilayer, which is beneficial for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, neutral charge, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 70

**SMILES:** C1=CC=C2C(=C1)C(=CC=N2)C(=O)NC3=CC=C(C=C3)S(=O)(=O)NC4=NC=CS4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex aromatic amide with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the quinoline and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the aromatic rings can help to stabilize the molecule within the membrane, potentially offsetting this effect.

3. **Polarity**: The molecule contains polar functional groups, such as the amide linkage and the thiazole ring. These groups can form hydrogen bonds, which may facilitate interactions with the aqueous environment and the membrane surface, potentially improving permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility required for passage through the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its lipophilicity and facilitate interactions with the lipid bilayer, promoting permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a favorable affinity for both the aqueous phase and the lipid bilayer, which is generally desirable for good permeability.

Overall, the given molecule's combination of lipophilic aromatic rings, polar functional groups, and neutral charge suggests that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 71

**SMILES:** C1=CC=C(C=C1)C2=NC=CC(=C2)C(=O)NC3=CC=C(C=C3)S(=O)(=O)NC4=NC=CS4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is an aromatic amide with several structural features that influence its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane, as lipophilic compounds tend to dissolve better in lipid environments.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434.35 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may allow for specific interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is a result of the aromatic rings and the amide linkage. This low polarity can enhance its permeability, as it allows the molecule to interact favorably with the hydrophobic regions of the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability. Charged molecules often have reduced permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The aromatic rings and heterocycles contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the flexibility required for the molecule to fit into the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its lipophilicity and ability to interact with the lipid bilayer through π-π interactions, which can further improve permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it can easily transition from an aqueous environment to a lipid environment, enhancing its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule exhibits several structural features that suggest high permeability in the PAMPA assay, including its lipophilicity, aromaticity, rigidity, and neutral charge.

Final answer: High permeability

------
# 72

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=CN=C2)C(=O)NC3=CC=C(C=C3)C4=NNN=N4

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex aromatic amide with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and phenyl groups, contributes to the lipophilic nature of the molecule. Aromatic rings are known to enhance lipophilicity, which can increase membrane permeability up to a certain point.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and a large molecular framework may limit its permeability due to steric hindrance.

3. **Polarity**: The molecule contains a sulfonamide group, which introduces polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity. The presence of a polar amide group also contributes to the molecule's ability to form hydrogen bonds, which can affect its interaction with the membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings impart a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic nature of the molecule enhances its lipophilicity and may facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide and amide, may lead to moderate hydration energy, which can influence the molecule's solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, size, and polarity, along with the presence of aromatic and polar groups, suggests that while it may have some difficulty due to size, it should still demonstrate reasonable permeability.

Final answer: Low-to-moderate permeability

------
# 73

**SMILES:** COC1=CC=CC(=C1O)CNC2=CC=C(C=C2)S(=O)(=O)NC3=CC=C(C=C3)N4CCNCC4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and functional groups. This complexity can lead to a moderate molecular size, which may affect its permeability. Larger molecules often have lower permeability due to steric hindrance and difficulty in crossing the membrane.

3. **Polarity**: The molecule contains several polar functional groups, including sulfonamide, hydroxyl, and amino groups. These groups can form hydrogen bonds, which may increase the molecule's affinity for the aqueous phase and reduce its overall lipophilicity. However, the balance between these polar and non-polar regions will determine its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and influence the molecule's interaction with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The polar functional groups suggest that the molecule may have a moderate hydration energy, which can affect its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests it may have a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilic and polar characteristics, along with its structural rigidity and aromaticity, supports its ability to traverse the artificial membrane, but the presence of multiple functional groups may also introduce some limitations.

Final answer: Low-to-moderate permeability

------
# 74

**SMILES:** C1CN(CCN1)C2=CC=C(C=C2)N[S+](=O)(C3=CC=C(C=C3)NCC4=C(C(=CC=C4)Cl)O)[O-]

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and functional groups. This complexity can lead to a moderate molecular size, which may affect its permeability. Larger molecules often have lower permeability due to size constraints.

3. **Polarity**: The molecule contains several polar functional groups, including the sulfonamide group, the hydroxyl group, and the piperazine ring. These groups can increase the polarity of the molecule, which may reduce its permeability through the hydrophobic membrane. However, the overall balance between lipophilicity and polarity will determine its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation during passage.

6. **Aromaticity**: The presence of multiple aromatic rings can also influence the molecule's interaction with the lipid bilayer, potentially enhancing its permeability through hydrophobic interactions.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have a moderate hydration energy, which can affect its permeability. Lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and neutral charge, as well as its structural features that promote membrane interaction.

Final answer: High permeability

------
# 75

**SMILES:** C1=CC=C2C=C(C=CC2=C1)CC(=O)NC3=CC=C(C=C3)S(=O)(=O)NC4=NC=CS4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the naphthalene and thiazole moieties, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The sulfamoyl group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall structure is dominated by aromatic and hydrophobic components, suggesting that the molecule's polarity is not a significant barrier to permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the thiazole ring contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows for more efficient interaction with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can also influence the molecule's interaction with the membrane, potentially enhancing lipophilic interactions and permeability.

7. **Hydration Energy**: The aromatic and hydrophobic nature of the molecule suggests that it has a relatively low hydration energy, which can facilitate its passage through the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is generally beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and structural rigidity, balanced by moderate polarity and a neutral charge.

Final answer: High permeability

------
# 76

**SMILES:** C1CNCCC1C2=CC=C(C=C2)N[S+](=O)(C3=CC=C(C=C3)NCC4=C(C=C(C=C4)Br)O)[O-]

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups and the bromophenyl moiety, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a sulfonamide group. This complexity can lead to a moderate molecular size, which may limit its permeability compared to smaller molecules. However, the presence of a piperidine ring can help reduce steric hindrance and improve permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall structure, dominated by aromatic rings, suggests that the molecule's polar surface area is not excessively high, which might favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the piperidine ring contribute to a relatively rigid structure, which can enhance the molecule's ability to permeate the membrane by reducing conformational flexibility.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer, potentially enhancing permeability through hydrophobic interactions.

7. **Hydration Energy**: The presence of hydroxyl and sulfonamide groups can lead to moderate hydration energy, which may impact the molecule's ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its moderate lipophilicity, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 77

**SMILES:** C1CNCCC1C2=CC=C(C=C2)N[S+](=O)(C3=CC=C(C=C3)NCC4=C(C=C(C=C4)Cl)O)[O-]

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane, as lipophilic compounds tend to dissolve better in lipid environments.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains several polar functional groups, including the sulfonamide and hydroxyl groups. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but can also hinder permeability through the lipid bilayer. However, the overall balance of these polar groups with the lipophilic aromatic rings suggests moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate permeation by allowing the molecule to maintain a stable conformation as it passes through the membrane.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and may also facilitate interactions with the lipid bilayer through π-π interactions, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can affect its permeability. Lower hydration energy generally improves membrane permeation, but the overall effect depends on the balance with lipophilicity.

8. **Membrane Affinity**: The given molecule appears to have a balanced affinity for both the aqueous and lipid phases, as indicated by its structural features. This balance is crucial for optimal permeability in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and structural rigidity suggests that it can traverse the artificial membrane, but the size and complexity may limit its permeability compared to smaller or less complex molecules.

Final answer: Low-to-moderate permeability

------
# 78

**SMILES:** CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)[C@H](C)C5=CC=CC=N5)OC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of methoxy and methyl groups contributes to the lipophilic character of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a pyridine ring, which introduces some degree of polarity. However, the overall polarity is balanced by the lipophilic methoxy and methyl groups, suggesting moderate polarity. This balance can favor moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The imidazoquinoline core provides a rigid structure, which can facilitate passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The presence of aromatic rings, such as the pyridine and imidazoquinoline, can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule's structural features suggest that it would exhibit moderate to high permeability in the PAMPA assay, balancing lipophilicity, size, and polarity to interact effectively with the artificial membrane.

Final answer: Moderate permeability.

------
# 79

**SMILES:** CC(C)(C)C1=CC=C(C=C1)C(=O)NC2=CN3C=C(C=CC3=N2)N4C=CN=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a tert-butyl group, which is a bulky hydrophobic moiety, contributes to the lipophilicity of the molecule. This group can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Aromaticity**: The molecule contains an imidazo[1,2-a]pyridine moiety and a phenyl ring. Aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, which may enhance permeability. However, the balance between hydrophobic and hydrophilic interactions will determine the overall permeability.

3. **Polarity**: The molecule has a benzamide group, which introduces some degree of polarity. The amide linkage can form hydrogen bonds, which may affect the molecule's interaction with the membrane. While this could reduce permeability, the overall effect will depend on the balance with other hydrophobic groups.

4. **Charge**: The molecule is described as a neutral compound, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

6. **Rigidity**: The presence of multiple aromatic rings and heterocyclic structures contributes to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows for more effective interaction with the lipid bilayer.

7. **Hydration Energy**: The molecule's structure suggests it may have a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The combination of hydrophobic and hydrophilic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity, which facilitate its interaction with the artificial membrane.

Final answer: High permeability

------
# 80

**SMILES:** COC1=CC=CC(=C1O)CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC=C(S3)C4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups and the thiazole ring, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple aromatic rings and heteroatoms, which may increase its molecular weight. However, the presence of a thiazole ring and a sulfonamide group can also contribute to a compact structure, potentially mitigating the effect of size on permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by aromatic and hydrophobic components. The presence of methoxy and hydroxy groups can also contribute to hydrogen bonding, which may affect the polarity and solubility of the molecule.

4. **Charge**: The given molecule is neutral, which is typical for many sulfonamides. This neutrality allows it to traverse lipid membranes more effectively compared to charged molecules.

5. **Rigidity**: The aromatic rings and the thiazole ring contribute to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic nature of the molecule can influence its interaction with the lipid bilayer, potentially enhancing its permeability due to favorable hydrophobic interactions.

7. **Hydration Energy**: The presence of polar groups, such as the hydroxy and sulfonamide groups, may lead to moderate hydration energy, which can affect the molecule's ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the given molecule suggests that it may have a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for membrane permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, structural rigidity, and balanced polarity.

Final answer: High permeability

------
# 81

**SMILES:** COC1=CC=CC(=C1O)CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC4=CC=CC=C4O3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzene and benzoxazole rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a complex structure that includes multiple aromatic rings and a benzoxazole moiety. This size can potentially limit its permeability due to steric hindrance, but the presence of lipophilic aromatic systems may still allow for significant permeation.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic systems. The presence of a methoxy group and a hydroxyl group on the phenyl ring also contributes to the polarity, which may reduce the overall permeability compared to a purely hydrophobic molecule.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the benzoxazole moiety contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and conformational changes.

6. **Aromaticity**: The aromatic systems can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the hydroxyl and sulfonamide groups, may lead to moderate hydration energy, which can affect membrane permeation.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic aromatic systems, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 82

**SMILES:** C1=CC=C(C(=C1)S(=O)(=O)NC2=C(C=CN=C2)C(=O)NC3=NC(=CS3)C4=CC=C(C=C4)F)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The given molecule contains several aromatic rings, including a chlorophenyl group and a pyrazole ring, which contribute to its lipophilic nature. The presence of a sulfonamide group, which is polar, can balance this by providing some hydrophilicity. Overall, the molecule is likely to have moderate lipophilicity, which is beneficial for permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple rings and functional groups. This complexity can lead to a moderate molecular weight, which may not hinder permeability but could limit it if the molecule is too large.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and the sulfonamide group. This low polar surface area is generally associated with higher permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles contributes to the rigidity of the molecule. Rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings in the molecule can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups like the sulfonamide and the fluorine atom can lower the hydration energy, making it easier for the molecule to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its moderate lipophilicity, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 83

**SMILES:** C1=CC=C2C(=C1)C(=NC(=N2)C3=CC=NC=C3)NC4=CC(=C(C=C4)C5=CC(=CC=C5)OC(F)(F)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinazoline derivative with several functional groups and structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the quinazoline core and the phenyl groups, contributes to the lipophilic nature of the molecule. The trifluoromethoxy group further enhances lipophilicity due to the electron-withdrawing nature of the trifluoromethyl group, which can increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of multiple aromatic rings can help to maintain a planar structure, potentially mitigating this effect.

3. **Polarity**: The molecule has a low polar surface area due to the absence of multiple polar functional groups. The trifluoromethoxy group introduces some polarity, but the overall structure is dominated by non-polar aromatic rings, which favor membrane permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The quinazoline core and the aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the structural features of the given molecule, such as its lipophilicity, rigidity, and aromaticity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 84

**SMILES:** C1CCN(CC1)CCOC2=CC=CC(=C2)C3=NNC4=C3C=C(C=C4)C5=NC=NN5

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several functional groups and aromatic systems, which influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the indazole and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The overall size of the molecule, including the piperidine ring and the indazole core, suggests a moderate molecular weight. While larger molecules can have reduced permeability, the specific arrangement of these groups may still allow for sufficient diffusion through the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic rings and the absence of highly polar functional groups. This low polarity can enhance its permeability by reducing interactions with the aqueous environment and increasing interactions with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indazole and phenyl rings contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the flexibility required for the molecule to fit into the lipid bilayer.

6. **Aromaticity**: The aromatic systems present in the molecule can enhance lipophilicity and may also participate in π-π interactions with the membrane, potentially aiding in permeation.

7. **Hydration Energy**: The lack of highly polar or charged groups suggests that the molecule has a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to remove water molecules from its surface.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that suggest it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 85

**SMILES:** CC[C@@H](C(=O)N1C[C@H](C[C@@H]1CC2=C(NC3=C2C=CC(=C3)F)C4=C(C5=C(N4)C=C(C=C5)F)C[C@@H]6C[C@@H](CN6C(=O)[C@H](CC)NC(=O)[C@H](C)NC)O)O)NC(=O)[C@H](C)NC

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the PAMPA assay, we need to consider its structural features and how they relate to the permeability characteristics mentioned earlier.

1. **Lipophilicity**: The given molecule contains several aromatic rings and fluorine atoms, which contribute to its lipophilic nature. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple rings and functional groups. While it is not excessively large, its size may limit its permeability due to steric hindrance and potential difficulty in passing through the membrane.

3. **Polarity**: The presence of fluorine atoms and multiple nitrogen-containing groups suggests a moderate level of polarity. However, the overall structure is dominated by hydrophobic aromatic rings, indicating that the molecule's polarity might not significantly hinder its permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings suggests a degree of rigidity, which can facilitate permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and may enhance its ability to interact with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of fluorine and nitrogen groups may lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests it has a favorable membrane affinity, which is beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

------
# 86

**SMILES:** CN(C)CCN1C(=O)C2=CC=CC3=CC(=CC(=C32)C1=O)N

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a member of the isoquinoline family, which is known for its aromatic and heterocyclic structure. This structural feature contributes to its potential permeability characteristics.

1. **Lipophilicity**: The presence of the isoquinoline core, which is aromatic, suggests that the given molecule has a degree of lipophilicity. Aromatic systems are generally lipophilic, which can enhance membrane permeability up to a certain point.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple functional groups, which may increase its molecular weight. This could potentially limit its permeability due to size constraints, as larger molecules may have difficulty traversing the lipid bilayer.

3. **Polarity**: The molecule contains an amino group and a dimethylaminoethyl side chain, which introduce polar characteristics. However, the overall polar surface area is relatively low compared to the aromatic and hydrophobic regions, suggesting that the molecule might still exhibit moderate lipophilicity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The isoquinoline core provides a rigid structure, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic nature of the isoquinoline ring system can enhance lipophilicity and may also facilitate interactions with the lipid bilayer through π-π interactions.

7. **Hydration Energy**: The presence of polar groups may lead to moderate hydration energy, which can influence the molecule's ability to permeate the membrane by affecting its solubility and interaction with the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it may have a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases of the membrane.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between hydrophilic and hydrophobic interactions with the artificial membrane.

Final answer: Low-to-moderate permeability

------
# 87

**SMILES:** C1CNCCC1(C2=CC=C(C=C2)C3=CNN=C3)C4=CC=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a phenylpyridine, which is characterized by a pyridine ring attached to a phenyl group. This structure suggests that the molecule has a degree of aromaticity and potential for π-π interactions, which can influence its permeability.

The presence of the pyridine ring indicates that the molecule has some polar characteristics, which can affect its solubility and interaction with the artificial membrane. However, the overall structure is dominated by aromatic rings, which contribute to its lipophilicity. This suggests that the molecule may have moderate to high permeability due to its ability to interact with the lipid components of the membrane.

Additionally, the presence of a chlorophenyl group introduces a chlorine atom, which can enhance lipophilicity and potentially improve membrane permeability by increasing the molecule's ability to penetrate lipid bilayers.

Overall, considering the balance of aromaticity, lipophilicity, and polar characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 88

**SMILES:** CN1C2=CN=C3C=CC(=CC3=C2N(C1=O)C4=CC(=C(C=C4)N5CCNCC5)C(F)(F)F)C6=CN=C(C=C6)OC

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the trifluoromethylphenyl and pyridinyl groups, contributes to the lipophilic nature of the molecule. The trifluoromethyl group is particularly known for enhancing lipophilicity due to its strong electron-withdrawing properties, which can increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains several polar groups, such as the piperazine ring and the pyridinyl group. These groups can form hydrogen bonds, which may enhance solubility in aqueous environments but can also hinder permeability through the lipid bilayer. However, the overall low polar surface area and the presence of non-polar groups suggest that the molecule may still exhibit moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with polar head groups of the membrane.

5. **Rigidity**: The imidazoquinoline core provides a rigid structure, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the trifluoromethyl group and other non-polar groups likely results in a lower hydration energy, which can improve membrane permeation by reducing the energy required to pass through the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and polar interactions.

Final answer: Low-to-moderate permeability

------
# 89

**SMILES:** C1=CC=C(C=C1)C2=NC=C(N2)C(=O)NC3=NC=C(S3)CC4=CC=C(C=C4)C(F)(F)F

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and trifluoromethylphenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of heterocyclic rings like the imidazole and thiazole can provide some flexibility and conformational adaptability, which might mitigate this effect.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of aromatic rings and the trifluoromethyl group, which is known for its electron-withdrawing properties. This suggests that the molecule is relatively non-polar, enhancing its permeability through the lipid-rich environment of the membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and heterocyclic structures contribute to a certain degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The trifluoromethyl group can lower the hydration energy of the molecule, making it easier for the molecule to traverse the aqueous environment surrounding the membrane and interact with the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is beneficial for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and favorable balance of hydrophobic and hydrophilic interactions.

Final answer: High permeability

------
# 90

**SMILES:** CC1=C(NC(=C1C(=O)C)C)C(=O)NC2=CC(=C(C=C2)OC)[S+](=O)(NC3=CC=CC=C3C#N)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features.

1. **Lipophilicity**: The presence of aromatic rings, such as the acetylphenyl and methoxyphenyl groups, contributes to the lipophilicity of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a potential for high permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple functional groups and aromatic rings. While size can be a limiting factor for permeability, the presence of these groups may also facilitate interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The sulfonamide group is polar, which can influence the molecule's solubility and permeability. However, the overall balance of polar and non-polar groups in the molecule suggests that it may still exhibit moderate permeability due to the presence of both polar and non-polar regions.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings and the pyrrole moiety contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic systems in the molecule can further enhance its lipophilicity and facilitate interactions with the membrane, potentially leading to high permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it may have moderate hydration energy, which can influence its permeability by affecting its interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The given molecule appears to have a balanced affinity for both the aqueous phase and the lipid bilayer, which is indicative of good permeability in the PAMPA assay.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 91

**SMILES:** C1=CC(=CC(=C1)C(=O)NCCO)C2=CC(=NC=N2)NC3=CC=C(C=C3)OC(F)(F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyrimidine rings, contributes to the lipophilic nature of the molecule. These rings can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.38 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and functional groups may allow for specific interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule contains several polar groups, including the hydroxyethyl group and the trifluoromethoxy group. These groups can form hydrogen bonds and increase the molecule's solubility in water, which may enhance its permeability. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the flexibility required for the molecule to fit into the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can influence its permeability by affecting its interaction with water molecules in the aqueous phase.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and structural rigidity.

Final answer: High permeability

------
# 92

**SMILES:** CC1=C(NC(=C1C(=O)C)C)C(=O)NC2=CC(=C(C=C2)OCCCN(C)C)[S+](=O)(NC3=CC=C(C=C3)Br)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of acetyl and dimethylamino groups contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of aromatic and heterocyclic rings, such as the pyrrole ring, can help to maintain a balance between size and permeability. The pyrrole ring is a planar, aromatic structure that can facilitate interactions with the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar groups like acetyl and dimethylamino. This low polarity can enhance its ability to permeate the lipid bilayer, as it reduces the energy required for the molecule to transition from an aqueous environment to a lipid environment.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings and the pyrrole structure contribute to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings, such as the bromophenyl group, can influence the molecule's lipophilicity and its ability to interact with the membrane. Aromatic rings can engage in π-π interactions with the aromatic residues in the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less tightly bound to water molecules, which can facilitate its passage through the membrane by reducing the energy required to remove water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Overall, the given molecule exhibits a combination of lipophilic, aromatic, and rigid characteristics that are conducive to high permeability in the PAMPA assay. Its structural features suggest that it can effectively interact with the artificial membrane, facilitating its passage through the lipid bilayer.

Final answer: High permeability

------
# 93

**SMILES:** C1CC1(C2=CC=C(C=C2)NC(=O)C3=CC(=NC=C3)C4=NC=CC(=C4)C(=O)O)N

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to the permeability characteristics mentioned earlier.

1. **Lipophilicity**: The given molecule contains aromatic rings and a pyridine moiety, which contribute to its lipophilic nature. This suggests that the molecule may have a moderate to high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule is relatively small, with a molecular weight of 342.35 g/mol. This size suggests that it may have higher permeability due to its ability to traverse the artificial membrane more easily compared to larger molecules.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of aromatic rings and the absence of highly polar functional groups. This low polarity can enhance its permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The presence of aromatic rings and a pyridine moiety contributes to the rigidity of the molecule. This rigidity can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the structure can enhance lipophilicity and influence interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The given molecule has a low hydration energy, which suggests that it can easily overcome the hydration shell surrounding the membrane, enhancing its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, size, polarity, charge, rigidity, and membrane affinity.

Final answer: High permeability

------
# 94

**SMILES:** C1CC(CCC1CC(=O)O)C2=CC=C(C=C2)N3CCOC4=NC=NC(=C4C3=O)N

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl and pyrano[2,3-d]pyrimidinyl groups, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The cyclohexyl group and the overall size of the molecule may contribute to moderate permeability. While larger molecules can have reduced permeability due to size constraints, the cyclohexyl group provides a degree of flexibility and conformational adaptability that may still allow the molecule to permeate the membrane effectively.

3. **Polarity**: The presence of an amino group and a carboxylic acid group introduces polar characteristics to the molecule. However, the overall polar surface area is relatively low due to the dominance of aromatic and hydrocarbon components, which may still favor moderate permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The aromatic rings contribute to a degree of rigidity, which can enhance the molecule's ability to permeate the membrane by maintaining a stable conformation during passage through the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability by stabilizing the interaction with the membrane.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the hydration energy is not excessively high, which can facilitate membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests a favorable membrane affinity, which is conducive to high permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, moderate size, neutral charge, and favorable balance of polar and non-polar characteristics.

Final answer: High permeability

------
# 95

**SMILES:** CC[C@@H](C1=CC=CC=C1)NC(=O)C2=C(C(=NC3=CC=CC=C32)C4=CC=CC=C4)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a phenyl group and a quinoline moiety contributes to the lipophilic nature of the molecule. These aromatic rings increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 343.3 g/mol. While size is a limiting factor for permeability, the presence of aromatic rings and a carboxamide group may help to maintain some degree of flexibility, potentially mitigating the negative effects of size.

3. **Polarity**: The molecule contains a hydroxyl group and a carboxamide group, which introduce polar characteristics. However, the overall polar surface area is relatively low due to the dominance of the aromatic and hydrocarbon portions. This balance suggests moderate polarity, which can facilitate membrane permeation.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid bilayers.

5. **Rigidity**: The quinoline and phenyl rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the structure can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the hydroxyl and carboxamide may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate polarity, and balanced affinity for the membrane.

Final answer: High permeability

------
# 96

**SMILES:** COC(=O)CNC(=O)C1=NC(=C2N1C=CN=C2)C3=CC=C(C=C3)[S+](=O)(C)[O-]

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl group and the imidazo[1,2-a]pyridine moiety, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a methylsulfonyl group, which introduces a polar character. However, the overall polarity is balanced by the lipophilic aromatic systems, suggesting moderate polarity. The presence of a polar group can enhance solubility in the aqueous phase, but it may also hinder permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged species typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The imidazo[1,2-a]pyridine core provides a rigid structure, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the methylsulfonyl and ester functionalities, may lead to moderate hydration energy. This can affect the molecule's ability to permeate the membrane, as lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and structural rigidity suggests that while it may have some difficulty permeating the membrane due to its size, its aromatic and polar features can facilitate interactions with the lipid bilayer.

Final answer: Low-to-moderate permeability

------
# 97

**SMILES:** C[S+](=O)(C1=CC=C(C=C1)C2=C3C=CC=CN3C(=N2)C(=O)N4CCOCC4)[O-]

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Imidazo[1,2-a]pyridine Core**: This bicyclic structure is relatively rigid and aromatic, which can enhance lipophilicity and membrane affinity. The presence of this core suggests that the molecule may have moderate to high permeability due to its ability to interact with the lipid bilayer.

2. **Morpholine Ring**: The morpholine moiety is a polar, heterocyclic amine that can increase the molecule's solubility in water. However, its presence also introduces a polar character, which can balance the lipophilicity of the imidazo[1,2-a]pyridine core. This balance can lead to moderate permeability, as the molecule can interact with both the aqueous and lipid phases.

3. **Methanone Linkage**: The carbonyl group in the methanone linkage can participate in hydrogen bonding, which may enhance interactions with the membrane. However, the overall effect on permeability will depend on the balance with other polar and non-polar groups in the molecule.

4. **Methylsulfonyl Group**: This group is highly polar and can increase the molecule's solubility in water. It may also contribute to the overall polarity of the molecule, potentially reducing permeability due to increased hydrophilicity.

5. **Overall Molecular Properties**: The given molecule has a relatively large molecular size and weight, which may limit its permeability. However, the presence of aromatic and rigid structures, along with a balance of polar and non-polar groups, suggests that it may still exhibit moderate permeability.

In summary, the given molecule's permeability is likely influenced by its aromatic and rigid imidazo[1,2-a]pyridine core, balanced by the polar morpholine and methylsulfonyl groups. This combination suggests moderate permeability, with the potential for some limitations due to the molecule's size and polarity.

Final answer: Low-to-moderate permeability

------
# 98

**SMILES:** CCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCOP(=O)(O)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrazolo[1,5-a]pyrimidine and fluorophenyl groups, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434.38 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heteroatoms may allow for some flexibility and conformational adaptability, which can mitigate the negative effects of size.

3. **Polarity**: The molecule contains several polar groups, including the phosphate group, amine, and ether linkages. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting that the molecule may have a moderate polar surface area.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to a degree of rigidity, which can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have a moderate hydration energy, which can influence its interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic groups suggests that the molecule has a balanced affinity for both phases, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable structural features for membrane interaction.

Final answer: High permeability

------
# 99

**SMILES:** C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=C(C=C4)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chromenone core, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a morpholine ring, which introduces some degree of polarity. However, the overall structure is dominated by aromatic and lipophilic components, suggesting that the molecule's polarity might not significantly hinder its permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The chromenone structure provides a rigid framework, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and may also participate in π-π interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the morpholine ring and other polar groups may reduce the hydration energy of the molecule, aiding in its permeation through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its lipophilic aromatic rings, moderate polarity, and neutral charge.

Final answer: High permeability

------
# 100

**SMILES:** COC1=CC=CC(=C1)N2C(=CC(=N2)C(=O)O)C3=CC(=C(C=C3)C4CCCCC4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and chlorophenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule contains multiple rings, including a cyclohexyl group and a pyrazole ring. These contribute to a relatively large molecular size and weight. While larger molecules can have reduced permeability due to size limitations, the specific arrangement and rigidity of these rings may allow for sufficient permeation.

3. **Polarity**: The molecule has a methoxy group and a carboxylic acid group, which introduce polar characteristics. The methoxy group can increase solubility in the aqueous phase, while the carboxylic acid group can form hydrogen bonds. However, the overall polar surface area is relatively low compared to the hydrophobic surface area, suggesting moderate polarity.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The presence of multiple aromatic and cyclohexyl rings imparts a degree of rigidity to the molecule. This rigidity can facilitate passage through the membrane by reducing the flexibility required for the molecule to fit into the lipid bilayer.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the carboxylic acid and methoxy groups may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate polarity, and balanced affinity for both phases.

Final answer: High permeability

------
# 101

**SMILES:** CCN(C1CCC(CC1)N(C)CCOC)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C#CCN4CCOCC4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the PAMPA assay, we need to consider its structural features and how they relate to the permeability characteristics mentioned earlier.

1. **Lipophilicity**: The given molecule contains several lipophilic groups, such as the ethoxy and methoxy groups, as well as aromatic rings. These features suggest that the molecule is likely to have a high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.46 g/mol. While size is a factor in permeability, the presence of multiple functional groups and rings may allow for some flexibility, which could mitigate the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of non-polar groups like the ethoxy and methoxy groups. Additionally, the presence of low numbers of hydrogen bond donors and acceptors suggests that the molecule is relatively non-polar, which is favorable for permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings and a pyridinone moiety suggests a degree of rigidity, which can influence the molecule's ability to permeate the membrane. Rigidity can help the molecule maintain a specific conformation that may facilitate passage through the membrane.

6. **Aromaticity**: The aromatic rings present in the molecule can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The given molecule has a low hydration energy, which indicates that it is less likely to form strong interactions with water, facilitating its passage through the lipid-rich environment of the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typically favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and balanced structural features that facilitate membrane passage.

Final answer: High permeability

------
# 102

**SMILES:** CN1C=NC(=C1C2=CC=C(C=C2)OC)C3=NC=CC(=C3)C(=O)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a methoxyphenyl group and a pyridine ring contributes to the lipophilic nature of the molecule. These aromatic rings can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 314.3 g/mol. While size is a critical factor in permeability, the presence of aromatic rings and a carboxylic acid group may help the molecule maintain sufficient flexibility to traverse the membrane.

3. **Polarity**: The molecule contains a carboxylic acid group, which can introduce polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity. The carboxylic acid group can also form hydrogen bonds, which may aid in membrane interaction.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule. While rigidity can be beneficial for membrane permeability, the presence of a methoxy group introduces some flexibility, which may help the molecule adapt to the membrane structure.

6. **Aromaticity**: The aromatic rings in the structure can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups like the carboxylic acid and methoxy groups may lead to moderate hydration energy, which can influence the molecule's ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and neutral charge, which facilitate its interaction with the artificial membrane.

Final answer: High permeability

------
# 103

**SMILES:** CC1=C(C=CC(=C1)Cl)COC2=CC=NN2C3=NC=CC(=C3)C(=O)O

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chlorophenyl and pyrazole rings, contributes to the lipophilic nature of the molecule. The chloro substituent on the phenyl ring further enhances lipophilicity due to its electron-withdrawing nature, which can increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a carboxylic acid group, which introduces polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting that the molecule may have moderate polarity. The presence of a methoxy group also contributes to the molecule's polarity, but its effect is somewhat counterbalanced by the adjacent aromatic system.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The aromatic rings and the pyrazole moiety contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the carboxylic acid, suggests that the molecule may have moderate hydration energy. This can affect its solubility and permeability, with lower hydration energy generally improving membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and rigidity, along with the presence of functional groups that can interact with the membrane, suggests that it can traverse the artificial membrane, but may not have the highest permeability due to its size and the presence of polar groups.

Final answer: Low-to-moderate permeability

------
# 104

**SMILES:** C1CC(=O)NC1CNC(=O)C2=C3C=CNC3=CC(=N2)C4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl group and the indolizine moiety, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a moderate molecular size and weight, as indicated by its classification as a pyrrolidinone. This size is not excessively large, which may allow it to pass through the membrane without significant steric hindrance.

3. **Polarity**: The molecule contains a pyrrolidinone group, which introduces some degree of polarity. However, the overall structure is dominated by aromatic and hydrocarbon components, suggesting that the polar surface area is not high enough to significantly impede permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indolizine moiety contributes to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings in the structure can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the pyrrolidinone group may lower the hydration energy of the molecule, facilitating its passage through the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 105

**SMILES:** COCCNC(=O)C1=CC=C(C=C1)C2=NC=C3N2C=C(N=C3)C4=CC(=CC=C4)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and imidazo[1,2-a]pyridine moieties, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may allow for favorable interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of a relatively non-polar character. This low polarity can enhance its ability to permeate the lipid-rich environment of the artificial membrane, contributing to high permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of lipids.

5. **Rigidity**: The imidazo[1,2-a]pyridine and phenyl rings provide a rigid structure, which can facilitate passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also may engage in π-π interactions with the aromatic residues in the membrane, enhancing permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less likely to form strong interactions with water, which can facilitate its passage through the hydrophobic environment of the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that enhance its permeability through the artificial membrane, leading to a classification of high permeability in the PAMPA assay.

Final answer: High permeability

------
# 106

**SMILES:** CN1CCC(CC1)NC(=O)C2=NC3=C(N2C)C=C(C(=N3)C4=CC=CC=C4)C5=CC(=NC=C5)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridinyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a methoxy group and a piperazine ring, which introduce some degree of polarity. However, the overall structure is dominated by aromatic and hydrocarbon components, suggesting that the molecule's polarity is not high enough to significantly hinder its permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The presence of multiple aromatic rings contributes to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Hydration Energy**: The aromatic and hydrophobic nature of the molecule suggests that it has a relatively low hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the aqueous environment.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous phase and the lipid bilayer.

Overall, the given molecule's structural features, such as its aromaticity, lipophilicity, and rigidity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 107

**SMILES:** CC1=NC=CC(=C1)C2=CC3=C(N=C2C4=CC=CC=C4)N=C(N3C)C(=O)NCCN(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.3 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and heterocyclic structures may allow for some degree of flexibility and conformational adaptability, which can mitigate the negative effects of size.

3. **Polarity**: The molecule contains several polar functional groups, including the carboxamide and dimethylamino groups. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase and facilitate interactions with the polar head groups of the artificial membrane. However, the overall polar surface area is relatively low, suggesting that the molecule's lipophilicity might dominate its behavior in the PAMPA assay.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid bilayers due to their inability to interact favorably with the hydrophobic lipid tails.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles contributes to a degree of rigidity in the molecular structure. This rigidity can enhance the molecule's ability to fit into and interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the aromatic residues in the lipid bilayer, which may enhance its permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, as it contains both hydrophilic and hydrophobic regions. This balance can facilitate its passage through the membrane by allowing it to interact with both the aqueous and lipid phases.

8. **Membrane Affinity**: The combination of lipophilic and polar features suggests that the molecule has a balanced affinity for both phases, which is often desirable for good permeability in PAMPA assays.

Overall, the given molecule's structural features, including its lipophilicity, aromaticity, and balanced polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 108

**SMILES:** CN1CCCC1CCOC(C2=CC=CC=C2Cl)C3=CC4=NC=CC(=C4N3)C(=O)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chlorophenyl group and the indole moiety, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of smaller functional groups, such as the methoxyethyl linkage, may help to balance this effect.

3. **Polarity**: The molecule contains polar groups, such as the carboxylic acid and the pyrrolopyridine moiety, which can form hydrogen bonds. While these groups can increase solubility in aqueous environments, they may also hinder permeability through the lipid membrane. The balance between these polar and non-polar regions will determine the overall polarity of the molecule.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indole and pyrrolopyridine rings contribute to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to fit into the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can affect its interaction with the aqueous phase and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions suggests that the molecule has a balanced affinity for both phases, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 109

**SMILES:** CC1=NC2=C(N1)C=C(C=C2)C(=O)N3CCC4(CC3)CC5=C(C(=O)C4)N(N=C5)C(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the pyrazole and isoquinoline moieties, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and a complex structure, which may limit its permeability due to steric hindrance. However, the specific arrangement of functional groups and rings might allow for sufficient permeation.

3. **Polarity**: The molecule contains a pyrazole ring and an isoquinoline moiety, which contribute to its aromaticity and potential for π-π interactions. These features can influence its polarity and interaction with the membrane, potentially enhancing permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The presence of multiple aromatic rings and a spirocyclic structure suggests a degree of rigidity, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Hydration Energy**: The aromatic and spirocyclic nature of the molecule likely results in a lower hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases of the membrane.

Overall, the given molecule's structural features, including its lipophilicity, aromaticity, rigidity, and balanced polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 110

**SMILES:** C1C(C2=C(NC1=O)N=C(S2)N)C3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a thienopyridine derivative, which is characterized by a fused heterocyclic structure combining a thiophene and a pyridine ring. This structural motif is known for its potential biological activity and pharmacological properties.

Analyzing the properties of the given molecule:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl group and the heterocyclic rings, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate lipid membranes, suggesting a potential for high permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively compact due to the fused ring system, which may allow for sufficient permeability through the artificial membrane, as larger molecules often face steric hindrance.

3. **Polarity**: The molecule contains an amino group, which can introduce some degree of polarity. However, the overall structure is dominated by the lipophilic aromatic rings, suggesting that the polar surface area is not high enough to significantly impede permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to traverse lipid bilayers.

5. **Rigidity**: The fused ring system imparts a degree of rigidity to the molecule, which can enhance its ability to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The phenyl group and the heterocyclic aromatic rings contribute to the molecule's lipophilicity and may facilitate interactions with the lipid membrane, enhancing permeability.

7. **Hydration Energy**: The presence of the heterocyclic rings and the amino group may lower the hydration energy of the molecule, making it easier for the molecule to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties suggests that the molecule has a favorable affinity for both the aqueous and lipid phases, which is beneficial for membrane permeability.

Overall, the given molecule is likely to exhibit high permeability in the Parallel Artificial Membrane Permeability Assay due to its lipophilic nature, compact structure, and favorable balance of polar and non-polar characteristics.

Final answer: High permeability

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# 111

**SMILES:** C1CN(CC2=C1N=C(N2)C3=CC=C(C=C3)C(=O)N)C(=O)CN4CCOCC4

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the imidazo[1,2-a]pyridine moiety, contributes to the lipophilic character of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the specific arrangement of its functional groups and rings might allow for sufficient permeation.

3. **Polarity**: The molecule contains a morpholine ring, which introduces some degree of polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The fused ring system, including the imidazo[1,2-a]pyridine and pyridine rings, contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the morpholine and amide, may lead to moderate hydration energy, which can affect the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of lipophilic and polar characteristics suggests that the molecule has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and polarity, and having a stable, rigid structure that facilitates membrane passage.

Final answer: Low-to-moderate permeability

------
# 112

**SMILES:** C1COCCN1CCNC(=O)C2CC(=O)N(C2)C3=NNC4=C3C=CC(=C4)Br

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a bromo-substituted indazole moiety contributes to the lipophilic character of the molecule. Bromine is a relatively large and electronegative atom, which can enhance lipophilicity due to its ability to participate in halogen bonding and increase the overall hydrophobicity of the molecule.

2. **Molecular Size and Weight**: The molecule contains a pyrrolidine-2-carboxamide moiety, which is relatively small and contributes to the overall molecular size. The presence of a pyrrolidine ring, a five-membered nitrogen-containing ring, can also influence the molecule's flexibility and conformational dynamics, potentially affecting its permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of the indazole and pyrrolidine rings, which are relatively non-polar. Additionally, the presence of a bromine atom and a nitro group can contribute to the overall polarity, but the balance between these groups and the non-polar regions suggests a moderate polar character.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indazole moiety provides a degree of rigidity to the molecule, which can enhance its ability to interact with the lipid bilayer in a specific orientation, potentially improving permeability.

6. **Aromaticity**: The indazole ring is aromatic, which can enhance lipophilicity and facilitate interactions with the lipid bilayer through π-π stacking and van der Waals interactions.

7. **Hydration Energy**: The presence of the nitro group and the overall structure of the molecule suggest a moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a good affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and favorable interactions with the lipid bilayer.

Final answer: High permeability

------
# 113

**SMILES:** CC1=NC=C2CNCCC2=C1CNC(=O)CN3C=NC4=CC=CC=C4C3=O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the quinazoline and pyrido[1,2-a]pyrimidine moieties, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The overall size of the molecule is relatively large due to the presence of multiple fused rings. While size is a factor in permeability, the specific arrangement of these rings and the presence of nitrogen atoms can create a balance that may still allow for sufficient permeability.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to a polar surface area. However, the overall structure is dominated by aromatic and heterocyclic systems, which are generally more lipophilic. This suggests that the polar surface area might not significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to traverse lipid membranes.

5. **Rigidity**: The fused ring systems impart a degree of rigidity to the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Hydration Energy**: The presence of nitrogen atoms and the overall structure may result in moderate hydration energy, which can influence the molecule's interaction with the aqueous and lipid phases, potentially supporting permeability.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Overall, the given molecule's structural features, such as its aromaticity, rigidity, and balanced polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 114

**SMILES:** C1CN(CC1NC(=O)C2=CC=CC=C2)C3=NNC(=C3)C4=CC=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chlorophenyl group contributes to the lipophilic nature of the molecule. This group is known for enhancing lipophilicity due to the electron-withdrawing chlorine atom, which can increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The molecule contains a pyrazolyl ring and a pyrrolidinyl moiety, which are relatively small and contribute to a moderate molecular weight. This size allows the molecule to fit within the membrane pores, potentially enhancing its permeability.

3. **Polarity**: The molecule has a benzamide group, which introduces some degree of polarity. However, the overall structure is dominated by the lipophilic aromatic and chlorinated phenyl groups, which likely outweigh the polar characteristics, contributing to higher permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings and the pyrazole moiety contribute to a certain degree of rigidity. This rigidity can facilitate the passage of the molecule through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl and pyrazole groups, can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy due to its aromatic and lipophilic components, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a favorable membrane affinity, which is essential for high permeability in the PAMPA assay.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, and structural rigidity.

Final answer: High permeability

------
# 115

**SMILES:** CC1=NC=C(C=C1)C(=O)N2CCC3=C(C2)N=C4C=C(NN4C3=O)C5=CC=CC=C5

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex heterocyclic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including a pyridine and a phenyl group, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and a complex structure, which may limit its permeability due to steric hindrance. However, the presence of multiple rings can also contribute to a more rigid structure, potentially aiding in permeability by allowing the molecule to fit more snugly into the membrane.

3. **Polarity**: The pyridine and carbonyl groups introduce some degree of polarity to the molecule. While this could reduce permeability, the overall lipophilicity due to the aromatic rings is likely to dominate, resulting in moderate to high permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The tricyclic structure of the given molecule contributes to its rigidity, which can enhance its ability to permeate the membrane by maintaining a consistent conformation.

6. **Aromaticity**: The aromatic rings, including the pyridine and phenyl groups, can interact with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the carbonyl, suggests that the given molecule may have moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of lipophilic and polar groups in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 116

**SMILES:** C1CN(CCC2=C1C(=O)NC(=N2)N3CCOCC3)CC4=C(C=CC(=C4)Cl)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl group substituted with chloro and fluoro substituents, contributes to the lipophilicity of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a morpholine ring, which introduces some degree of polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can favor moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The pyrimidopyrimidine core provides a degree of rigidity to the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the morpholine, may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and rigidity, along with the presence of aromatic and heterocyclic components, suggests that while it may have some challenges due to size, it should still be able to traverse the artificial membrane with reasonable efficiency.

Final answer: Low-to-moderate permeability

------
# 117

**SMILES:** C1CN(CCC2=C1C(=O)NC(=N2)N3CCOCC3)CC4=C(C=C(C=C4)Cl)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl group substituted with chloro and fluoro substituents, contributes to the lipophilicity of the molecule. These halogen atoms can enhance lipophilicity due to their electron-withdrawing properties, which may increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, with multiple rings and heteroatoms. This size can potentially limit its permeability due to steric hindrance and difficulty in navigating the lipid bilayer. However, the presence of a pyrimidinone core may help in maintaining a balance between size and permeability.

3. **Polarity**: The molecule contains a morpholine ring, which introduces some degree of polarity. However, the overall polarity is balanced by the lipophilic aromatic and halogenated groups, suggesting that the molecule may have moderate polarity, which can be favorable for permeability.

4. **Charge**: The molecule is neutral, which is generally beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by providing a stable conformation that can interact effectively with the lipid bilayer.

6. **Aromaticity**: The aromatic rings, including the phenyl and pyrimidinone moieties, can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the morpholine, may reduce the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a moderate affinity for both the aqueous and lipid phases, which is often desirable for good permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, rigidity, and polarity that facilitates its interaction with the artificial membrane.

Final answer: High permeability

------
# 118

**SMILES:** COC1=CC=C(C=C1)C(=O)N2CCCC(C2)C3=NN(C(=O)N3)C4=CC=C(C=C4)OC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of methoxy groups on the aromatic rings increases the lipophilicity of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The methoxy groups contribute to the overall polarity of the molecule, but the presence of aromatic rings and the triazolone moiety may balance this, resulting in a moderate polarity. This balance can facilitate membrane permeation by allowing the molecule to interact with both hydrophilic and hydrophobic environments.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The triazolone ring and the aromatic rings contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance the molecule's permeability by stabilizing its interaction with the membrane.

7. **Hydration Energy**: The presence of methoxy groups and the triazolone moiety may lower the hydration energy of the molecule, facilitating its passage through the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic components in the molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and structural rigidity, along with the presence of functional groups that facilitate membrane interactions, suggests that the molecule can traverse the artificial membrane with reasonable efficiency.

Final answer: Low-to-moderate permeability

------
# 119

**SMILES:** C1CN(CCC1C2=NN(C(=O)N2)C3=CC=C(C=C3)F)C(=O)C4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and fluorophenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and a piperidine ring may allow the molecule to fit within the membrane's lipid bilayer, potentially mitigating some of the size-related limitations.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of its overall non-polar character. This low polarity can enhance its ability to traverse the lipid-rich environment of the artificial membrane, contributing to higher permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid bilayers due to their inability to interact favorably with the hydrophobic environment.

5. **Rigidity**: The presence of multiple aromatic rings and a triazolone moiety introduces a degree of rigidity to the molecule. This rigidity can facilitate the molecule's passage through the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also play a role in the molecule's ability to engage in π-π interactions with the membrane, which can further enhance its permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less likely to form strong interactions with water, which can facilitate its passage through the membrane by reducing the energy required for desorption from the aqueous phase.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is conducive to high permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and favorable balance of hydrophobic and hydrophilic interactions.

Final answer: High permeability

------
# 120

**SMILES:** COC1=CC=C(C=C1)N2C(=O)NC(=N2)C3CCN(CC3)C(=O)C4CC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a methoxyphenyl group contributes to the lipophilic nature of the molecule. Methoxy groups are electron-donating, which can enhance the lipophilicity of the aromatic ring, potentially increasing the molecule's ability to permeate the lipid membrane.

2. **Molecular Size and Weight**: The molecule contains a piperidine ring and a triazolone moiety, which are relatively small and contribute to a moderate molecular size. This size is suitable for permeability, as it is neither too large nor too small. The cyclopropanecarbonyl group adds a small, rigid structure that may also contribute to permeability by reducing steric hindrance.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar groups like the methoxyphenyl and cyclopropanecarbonyl groups. This low polarity can enhance permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The cyclopropane ring introduces a degree of rigidity to the molecule. This rigidity can improve membrane permeability by reducing the flexibility of the molecule, which may otherwise hinder its passage through the membrane.

6. **Aromaticity**: The aromatic methoxyphenyl group can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, facilitating its passage through the lipid membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Overall, the given molecule exhibits a combination of lipophilicity, moderate size, low polarity, and structural rigidity, which collectively suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 121

**SMILES:** COC1=CC=C(C=C1)N2C(=O)NC(=N2)C3CCCN(C3)C(=O)C4=CC=CC=C4F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the fluorophenyl and methoxyphenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and heterocyclic structures may allow for some degree of flexibility, which can mitigate the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of its overall non-polar character. This low polarity can enhance its ability to traverse the lipid bilayer, as it is less likely to form strong interactions with water molecules.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a triazolone ring contributes to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less likely to form strong interactions with water, which can aid in its permeation through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and balanced affinity for both phases.

Final answer: High permeability

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# 122

**SMILES:** CCCS(=O)(=O)C1=NC(=CC(=N1)NC2CC2)C3=CC4=C(C=C3)N(C=C4)C5CC(NC(C5)(C)C)(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the pyridine and indole rings, contributes to the lipophilic nature of the molecule. Additionally, the tert-butyl groups attached to the piperazine and pyridine rings further enhance lipophilicity, which generally increases permeability up to a certain threshold.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of cyclic structures like the piperazine and pyrrolidine rings can help to maintain a certain degree of rigidity, which can aid in permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar groups like the tert-butyl and aromatic rings. This low polarity is associated with higher permeability as it allows the molecule to interact favorably with the lipid bilayer of the artificial membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged species typically have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The presence of multiple rings, such as the pyrrolidine and piperazine rings, contributes to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to permeate the membrane by reducing the flexibility required for passage.

6. **Aromaticity**: The indole and pyridine rings contribute to the aromatic character of the molecule, which can influence lipophilicity and interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the sulfonyl group can increase the hydration energy, which might reduce permeability. However, the overall structure suggests that this effect is balanced by the other lipophilic and rigid components.

8. **Membrane Affinity**: The molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is indicative of good permeability in the PAMPA assay.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, rigidity, and balanced polarity.

Final answer: High permeability

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# 123

**SMILES:** CC1=C(C(=NO1)C)C2=CC(=C(C=C2)C3=CC(=C(S3)NC(=O)N)C(=O)N)O[C@H]4CCNC4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to the properties that influence membrane permeability.

1. **Lipophilicity**: The given molecule contains several aromatic rings, including a thiophene and two phenyl rings, which contribute to its lipophilic character. The presence of these aromatic systems suggests that the molecule is likely to have a high lipophilicity, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The molecule is relatively complex, with multiple rings and functional groups. While the thiophene and phenyl rings contribute to a larger molecular size, the overall molecular weight is still moderate. This suggests that the molecule might have moderate permeability, as larger molecules can have reduced permeability due to size constraints.

3. **Polarity**: The molecule has a low polar surface area due to the presence of multiple aromatic rings and the absence of highly polar functional groups. This low polarity is associated with higher permeability, as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a thiophene ring contributes to a relatively rigid structure. This rigidity can enhance membrane permeability as it allows the molecule to maintain a consistent conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings in the molecule can influence its lipophilicity and interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The molecule's structure suggests a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate size, low polarity, and balanced structural features.

Final answer: High permeability

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# 124

**SMILES:** CC(C)C1=CC(=NN1)C(=O)N2CC[C@H](C2)NC(=O)C3CC3

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a cyclopropanecarbonyl group and a propan-2-yl group contributes to the lipophilic nature of the molecule. These groups increase the hydrophobic character, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 342.3 g/mol. While size is a limiting factor for permeability, the specific arrangement of functional groups and the presence of aromatic rings may allow for sufficient permeation.

3. **Polarity**: The molecule has a low polar surface area, which is a result of the non-polar cyclopropane and propan-2-yl groups. This low polarity contributes to higher permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The cyclopropane ring introduces a degree of rigidity to the molecule. This rigidity can enhance membrane permeability by reducing the flexibility of the molecule, which may otherwise hinder its passage through the membrane.

6. **Aromaticity**: The presence of a pyrazole ring introduces aromaticity, which can influence lipophilicity and molecular interactions with the lipid bilayer. Aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, facilitating its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests a moderate affinity for both the aqueous phase and the lipid bilayer, which is typically favorable for PAMPA permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and aromaticity, combined with a neutral charge and low polar surface area.

Final answer: High permeability

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# 125

**SMILES:** C[C@H](C1=NN=C2N1C=C(C=C2F)C3=CN(N=C3)C)N4C=CC5=C(C4=O)C=C(C=N5)OCCOC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the pyrazolo[4,3-b]pyridine and pyridine moieties, suggests a significant degree of lipophilicity. This is further enhanced by the fluorine atom, which can increase the molecule's lipophilicity due to its electronegativity and ability to participate in van der Waals interactions.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 394.37 g/mol. While size is a limiting factor for permeability, the presence of multiple rings and heteroatoms may allow for some flexibility and conformational adaptability, which can mitigate this effect to some extent.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of non-polar groups such as the methoxyethoxy chain. This contributes to its lipophilicity and enhances its ability to permeate the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The aromatic rings and heterocyclic structures contribute to a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic systems present in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The low hydration energy, as indicated by the molecule's solubility in organic solvents, suggests that it can easily transition from an aqueous environment to a lipid environment, facilitating membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay, as it possesses a combination of lipophilicity, structural rigidity, and favorable interactions with the lipid bilayer.

Final answer: High permeability

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# 126

**SMILES:** CCN1C(=NC(=N1)C2CCN(CC2)C(=O)CCO)C3=CN=C(C(=N3)C4=NN=C(O4)C(C)(C)C)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the pyrazolo[1,5-a][3,1,4]triazole and pyrazole rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of multiple rings and heteroatoms may allow for some flexibility and conformational adaptability, which can still facilitate passage through the membrane.

3. **Polarity**: The molecule contains several nitrogen atoms within its heterocyclic rings, which can contribute to polarity. However, the overall structure is dominated by aromatic and alkyl groups, suggesting a relatively low polar surface area. This could favor higher permeability.

4. **Charge**: The molecule is described as a neutral compound, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles introduces rigidity to the molecule. While rigidity can sometimes hinder permeability due to limited conformational flexibility, in this case, it may also enhance membrane affinity due to the stable planar structure.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of hydroxyl groups, such as the hydroxypropan-1-one moiety, can influence the hydration energy of the molecule. However, the overall structure suggests that the molecule may have a lower hydration energy, facilitating membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable interactions with the lipid bilayer.

Final answer: High permeability

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# 127

**SMILES:** C1CCN(C1)C(=O)[C@@H]2CCCN(C2)C3=NC4=C(C=C3)NC(=N4)C5(CC5)N6C=C(C=N6)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the pyrazolo[1,5-a]pyridine and pyridine moieties, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to its polarity. However, the overall structure, with its aromatic rings, suggests that the polar surface area is balanced by lipophilic regions, potentially allowing moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The presence of multiple aromatic rings and a cyclopropyl group introduces rigidity to the molecule. This rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous phase.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic regions in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, rigidity, and membrane affinity that facilitates its passage through the artificial membrane.

Final answer: High permeability

------
# 128

**SMILES:** C[C@@]1(C2=C(C=C(C=C2)C3=CNN=C3)C(=O)N1)C4=NC=NC=C4F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure with several functional groups and heterocycles that influence its permeability in the PAMPA assay. Let's analyze its properties:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrazole and fluoro-substituted indole, suggests that the molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of heterocycles like pyrazole and pyrimidine can help to balance this by providing rigidity and planarity, which can facilitate passage through the membrane.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of non-polar groups like the fluoro-substituted indole. This low polarity contributes to higher permeability as it allows the molecule to interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The indole and pyrazole rings provide a degree of rigidity to the molecule, which can enhance its ability to permeate the membrane by maintaining a consistent conformation that can interact effectively with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the indole and pyrazole rings can further enhance lipophilicity and facilitate interactions with the lipid bilayer, promoting permeability.

7. **Hydration Energy**: The presence of heterocycles like pyrimidine and fluoro groups can lower the hydration energy of the molecule, making it easier for the molecule to permeate the membrane by reducing its affinity for water.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule exhibits a combination of lipophilicity, rigidity, and balanced polarity that suggests it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 129

**SMILES:** CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)CCNC(C)C)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex polycyclic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings and a large polycyclic structure suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is a large and complex structure, which may limit its permeability due to size constraints. Larger molecules often have reduced permeability because they may not fit through the membrane pores easily.

3. **Polarity**: The molecule contains a hydroxy group and an ethyl group, which contribute to its polarity. However, the overall structure is dominated by the large aromatic and polycyclic system, which is more lipophilic. This balance suggests moderate polarity, which could allow for some degree of permeability but may be limited by the size of the molecule.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The polycyclic structure of the given molecule contributes to its rigidity. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic rings can increase lipophilicity and influence the molecule's ability to interact with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the hydroxy group may reduce the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule's structural features suggest that it would have moderate to high permeability in the PAMPA assay, with its lipophilicity, rigidity, and balanced polarity contributing to its ability to traverse the artificial membrane.

Final answer: High permeability

------
# 130

**SMILES:** COC1=CC=C(C=C1)C2=CC=C(O2)C(=O)NC3CC(C3)C4=CC(=O)NC(=N4)N

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of aromatic rings, such as the furan and pyrimidinyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The cyclobutyl group introduces some rigidity and bulk to the molecule. While this can affect permeability, the overall size and weight will depend on the entire molecular structure. The balance between rigidity and size will influence how well the molecule can traverse the membrane.

3. **Polarity**: The molecule contains polar groups such as the amino and oxo groups on the pyrimidinyl ring. However, the overall polar surface area is balanced by the lipophilic aromatic rings, which may allow for moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The cyclobutyl ring provides some rigidity, which can help the molecule maintain a stable conformation as it interacts with the membrane. This can enhance its permeability.

6. **Aromaticity**: The aromatic rings, including the furan and pyrimidinyl groups, can engage in π-π interactions with the lipid bilayer, potentially aiding in permeation.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can influence its interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule's structure suggests it would have moderate to high permeability in the artificial membrane, due to its balanced lipophilicity, moderate polarity, and structural rigidity.

Final answer: Moderate permeability.

------
# 131

**SMILES:** C[C@]12C[C@H]([C@@H]([C@@]1(CC(=O)[C@@]3([C@H]2CC=C4[C@H]3C=C(C(=O)C4(C)C)O)C)C)[C@](C)(C(=O)/C=C\C(C)(C)O)O)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methyl groups and a cyclopenta[a]phenanthrene core suggests a high degree of lipophilicity. This lipophilic nature is likely to enhance the molecule's ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, with a significant number of carbon atoms and rings. While size can be a limiting factor for permeability, the specific arrangement of rings and functional groups may allow for sufficient flexibility and conformational adaptability to traverse the membrane.

3. **Polarity**: The molecule contains several polar functional groups, including hydroxyl groups and ketones. These groups can form hydrogen bonds, which may facilitate interactions with the aqueous environment and the lipid bilayer. However, the overall polarity is balanced by the extensive hydrophobic framework, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged species typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The cyclopenta[a]phenanthrene structure imparts a certain degree of rigidity, which can influence the molecule's ability to fit into the membrane. Rigidity can both hinder and facilitate permeability depending on the fit with the membrane.

6. **Aromaticity**: The presence of aromatic rings contributes to the lipophilicity and may enhance interactions with the lipid bilayer through π-π interactions, potentially aiding in permeability.

7. **Hydration Energy**: The presence of hydroxyl groups and ketones suggests that the molecule may have moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its lipophilicity, balanced polarity, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 132

**SMILES:** CCC[C@@H](C1=CC=CC=C1)NC(=O)C(=CC2=NC(=CC=C2)Br)C#N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
To predict the permeability of the given molecule in the PAMPA assay, we need to consider its structural features and how they relate to the permeability characteristics mentioned.

1. **Lipophilicity**: The presence of a bromophenyl group and a pyridinyl group suggests that the given molecule has significant lipophilic character. These aromatic groups contribute to the overall hydrophobic nature, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple functional groups, including a phenyl ring, a pyridinyl ring, and a cyano group. While these groups add to the molecular weight, the overall size and weight are balanced by the linear nature of the but-2-enamide chain, which may still allow for sufficient permeability.

3. **Polarity**: The cyano group and the amide linkage introduce some degree of polarity. However, the overall polar surface area is relatively low due to the dominance of the aromatic rings, which can interact favorably with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced diffusion through lipid membranes.

5. **Rigidity**: The presence of aromatic rings and a conjugated system in the but-2-enamide chain contributes to the rigidity of the molecule. This rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The given molecule's structure suggests a relatively low hydration energy due to its hydrophobic and aromatic nature, which can facilitate membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests a favorable membrane affinity, which is conducive to high permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable structural characteristics for membrane interaction.

Final answer: High permeability

------
# 133

**SMILES:** C1=CC=C(C=C1)C2=CN=C(N=C2NC3=CC(=C(C=C3)F)F)C4=CC=NC=C4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex aromatic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as pyridine and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to its polarity. However, the overall structure is dominated by aromatic rings, which are hydrophobic. The balance between these polar and non-polar regions will influence its permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings provide a rigid structure, which can facilitate passage through the membrane by reducing the flexibility required for the molecule to fit into the membrane's structure.

6. **Aromaticity**: The presence of multiple aromatic systems can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The aromatic and heterocyclic nature of the molecule suggests it may have a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

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# 134

**SMILES:** CC(=O)N1CCC2=C(C1)SC3=C2C(=O)N(C(=O)N3CC4=CC(=CC=C4)C(F)(F)F)C5=CC=CC=C5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and trifluoromethylphenyl groups, contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, with multiple rings and functional groups. While size can be a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help to maintain a balance, allowing for sufficient permeability despite the size.

3. **Polarity**: The molecule contains several polar groups, such as the acetyl and carbonyl groups, which can form hydrogen bonds. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting that the polar surface area is not excessively high, which could favor moderate permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The tricyclic structure of the molecule contributes to its rigidity. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also may engage in π-π interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The presence of multiple heteroatoms (oxygen and nitrogen) and aromatic rings suggests that the molecule may have a moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and structural rigidity.

Final answer: High permeability

------
# 135

**SMILES:** C1=CC=C2C(=C1)C(=NC(=N2)C3=CC=NC=C3)NC4=CC(=C(C=C4)C5=C(C=C(C=C5)F)Cl)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinazoline derivative with several distinct structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine groups, contributes to the lipophilic nature of the molecule. The chloro and fluoro substituents on the phenyl ring further enhance lipophilicity due to their electron-withdrawing properties, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The quinazoline core and the attached aromatic rings contribute to a relatively large molecular size. While this can limit permeability due to steric hindrance, the presence of multiple aromatic systems can also facilitate interactions with the lipid bilayer, potentially offsetting this effect.

3. **Polarity**: The molecule has a low polar surface area due to the predominance of aromatic and halogenated groups, which are non-polar. This characteristic is favorable for permeability as it allows the molecule to interact more effectively with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes due to their inability to dissolve in the hydrophobic lipid environment.

5. **Rigidity**: The quinazoline core and the aromatic rings contribute to a rigid structure, which can enhance the molecule's ability to permeate the membrane by reducing the flexibility that might otherwise hinder passage through the lipid bilayer.

6. **Aromaticity**: The aromatic systems present in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The presence of halogen atoms and aromatic systems suggests that the hydration energy of the molecule is relatively low, facilitating its passage through the aqueous environment surrounding the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests a favorable membrane affinity, which is conducive to high permeability.

Overall, the structural features of the given molecule, including its lipophilicity, aromaticity, rigidity, and neutral charge, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 136

**SMILES:** C1CN(CCC1C#N)C2=NC(=CS2)C3=CC=C(C=C3)Br

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a bromophenyl group contributes to the lipophilic character of the molecule. Bromine is a halogen, which can enhance lipophilicity due to its electron-withdrawing nature. This suggests that the molecule may have a moderate to high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.5 g/mol. While size is a factor in permeability, the presence of multiple functional groups and rings may allow for specific interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule contains a piperidine ring, which is a secondary amine, contributing to its polar character. However, the overall polar surface area is relatively low due to the presence of aromatic rings and the bromine atom, which can balance the polarity. The presence of a nitrile group (carbonitrile) also adds to the polarity, but its impact is moderated by the surrounding lipophilic groups.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The thiazole ring and the aromatic phenyl ring contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings, including the phenyl and thiazole rings, can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have a moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous environment.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and structural rigidity.

Final answer: High permeability

------
# 137

**SMILES:** CC1=NOC(=C1S(=O)(=O)N2CCC(CC2)C(=O)NC3=CC=C(C=C3)C#N)/C=C/C4=CC=CC=C4F

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and nitrile-substituted phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a sulfonyl group, which is polar and can form hydrogen bonds. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can favor moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The presence of the oxazole ring introduces some rigidity to the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings contribute to the lipophilicity and can also participate in π-π interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonyl and amide groups, suggests that the molecule may have moderate hydration energy. This can affect its solubility and permeability, with lower hydration energy generally improving membrane permeation.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a balanced molecular size, and structural features that favor moderate to high permeability in the PAMPA assay.

Final answer: Low-to-moderate permeability

------
# 138

**SMILES:** CC(C)(C#N)C1=CC=C(C=C1)C2=NC=C(C=C2)CN3CCN(CC3)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings and a nitrile group suggests that the given molecule has a significant degree of lipophilicity. Aromatic rings contribute to the hydrophobic character, while the nitrile group can enhance lipophilicity due to its ability to participate in hydrophobic interactions.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 342.5 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and a nitrile group may allow for sufficient lipophilicity to overcome this size.

3. **Polarity**: The molecule has a low polar surface area, which is indicated by the presence of a nitrile group and aromatic rings. This low polarity suggests that the molecule can interact favorably with the lipid bilayer, enhancing its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings contributes to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Hydration Energy**: The nitrile group and aromatic rings suggest that the molecule has a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to break water interactions.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases.

Overall, the given molecule exhibits a combination of lipophilicity, rigidity, and favorable membrane interactions, which collectively suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

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# 139

**SMILES:** C1=CC=C(C(=C1)CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC=CS3)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively complex, with multiple aromatic rings and heterocyclic components. While the sulfonamide group is relatively small, the overall size and complexity may limit its permeability compared to simpler molecules.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall structure is balanced with lipophilic aromatic rings, which may mitigate this effect.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the thiazole moiety contribute to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The sulfonamide group and aromatic rings may contribute to a moderate hydration energy, which can influence the molecule's ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic components suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, neutral charge, and structural rigidity.

Final answer: High permeability

------
# 140

**SMILES:** COC1=CC2=C(C=C1)NC(=O)C(=C2)C3=NOC(=N3)C4=CC(=CC=C4)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several functional groups and ring systems, which influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Quinazoline Core**: The quinazoline moiety is a bicyclic aromatic system that contributes to the molecule's lipophilicity. Aromatic systems are generally associated with higher permeability due to their ability to interact with the lipid bilayer through π-π interactions.

2. **Methoxy Groups**: The presence of methoxy groups on the phenyl and quinazoline rings increases the lipophilicity of the molecule. Methoxy groups can enhance membrane permeability by increasing the molecule's ability to dissolve in the lipid phase of the membrane.

3. **Isoxazole Ring**: The isoxazole ring is a heterocyclic aromatic compound that can contribute to the molecule's overall rigidity and planarity. This rigidity can enhance the molecule's ability to permeate the membrane by reducing its flexibility and allowing it to fit more snugly into the lipid bilayer.

4. **Overall Aromaticity and Planarity**: The combination of aromatic rings and heterocycles in the given molecule suggests a high degree of planarity and aromaticity. This can facilitate interactions with the lipid bilayer, enhancing permeability.

5. **Lipophilicity and Polarity**: The balance of lipophilic and polar features in the given molecule suggests that it may have moderate to high permeability. The methoxy groups and aromatic rings increase lipophilicity, while the isoxazole and quinazoline rings provide some polar character.

6. **Charge and Solubility**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

In summary, the given molecule's structural features, including its aromaticity, methoxy groups, and heterocyclic rings, suggest that it would have high permeability in the PAMPA assay. These features enhance its ability to interact with the lipid bilayer, dissolve in the lipid phase, and permeate the membrane.

Final answer: High permeability

------
# 141

**SMILES:** CC1=C(C=C(C=C1)N2C3=NC=NC(=C3C=N2)NC(C)COC)C

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the dimethylphenyl group contributes to the lipophilic nature of the molecule. This group can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a pyrazolo[3,4-d]pyrimidine core, which is relatively polar. However, the overall polarity is balanced by the lipophilic dimethylphenyl group. The presence of nitrogen atoms in the pyrazolo and pyrimidine rings can also contribute to hydrogen bonding, which may affect permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The aromatic rings in the structure provide rigidity, which can enhance the molecule's ability to permeate the membrane by maintaining a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can also influence the lipophilicity and membrane interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the methoxy group and the amine linkage may contribute to the molecule's hydration energy, potentially affecting its interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic groups suggests that the molecule has a moderate affinity for both the aqueous phase and the lipid bilayer, which can favor its permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and rigidity, along with the presence of aromatic and heterocyclic components, suggests that it can interact effectively with the artificial membrane, but may be limited by its size and the presence of polar groups.

Final answer: Low-to-moderate permeability

------
# 142

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)N2C=C(C3=CC=CC=C32)C(=O)NC4=NC(=CS4)C5=CC=CC=C5

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and indole groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule contains multiple aromatic rings and a sulfonyl group, which can increase its molecular size and weight. While larger molecules generally have lower permeability, the specific arrangement and electronic properties of these groups can still allow for sufficient permeation.

3. **Polarity**: The sulfonyl group introduces a degree of polarity to the molecule, which can affect its solubility and interaction with the membrane. However, the overall structure, dominated by aromatic systems, suggests a balance that might not significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The indole and phenyl groups contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to fit into the membrane's lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic systems not only contribute to lipophilicity but also can participate in π-π interactions with the aromatic residues of the membrane, which may facilitate permeation.

7. **Hydration Energy**: The presence of sulfonyl and amide groups can influence the hydration energy of the molecule. While these groups can form hydrogen bonds, their presence in a larger, lipophilic framework might reduce the overall hydration energy, favoring membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a moderate affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 143

**SMILES:** CC1=C(C=C(C=C1)N2C3=NC=NC(=C3C=N2)NCCCN4C=CN=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chloro-substituted methylphenyl group contributes to the lipophilic nature of the molecule. This group can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule contains a pyrazolo[3,4-d]pyrimidine core, which is relatively rigid and contributes to the overall molecular size. While larger molecules generally have lower permeability due to size constraints, the rigidity of this core may help the molecule to fit into the membrane more efficiently.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the absence of multiple polar functional groups. This characteristic can enhance its ability to traverse the lipid bilayer, as it reduces the energy required for the molecule to overcome the hydrophobic barrier.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Aromaticity**: The presence of aromatic rings, such as the phenyl and pyrazolo[3,4-d]pyrimidine rings, can enhance lipophilicity and facilitate interactions with the lipid bilayer. These rings can also participate in π-π interactions with the membrane, potentially aiding in permeation.

6. **Hydration Energy**: The low hydration energy suggests that the molecule is less tightly bound to water molecules, which can enhance its ability to permeate the membrane by reducing the energy required to separate from the aqueous environment.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is conducive to high permeability.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that are likely to enhance its permeability in the PAMPA assay. These features collectively suggest that the molecule would have high permeability through the artificial membrane.

Final answer: High permeability

------
# 144

**SMILES:** CCN1CCN(CC1)C(=O)CCCN2C(=O)C3=NN(C(=C3C(=N2)C)C)C4=CC=C(C=C4)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methyl groups and a dimethylpyrazolopyridazinone core suggests a relatively high lipophilicity. This is likely to enhance the molecule's ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The overall size of the molecule, including the pyrazolopyridazinone core and the piperazine moiety, is relatively large. While this could potentially limit permeability due to steric hindrance, the presence of aromatic and aliphatic groups may facilitate membrane passage.

3. **Polarity**: The molecule has a low polar surface area due to the absence of multiple polar functional groups. This is beneficial for permeability as it allows the molecule to interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The molecule is neutral, which is advantageous for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The pyrazolopyridazinone core provides a degree of rigidity, which can enhance the molecule's ability to permeate the membrane by maintaining a consistent conformation that interacts effectively with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings, such as the pyrazolopyridazinone and the phenyl group, can influence lipophilicity and facilitate interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a favorable membrane affinity, which is likely to enhance its permeability.

Considering these structural features, the given molecule is expected to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, polarity, and structural rigidity.

Final answer: High permeability

------
# 145

**SMILES:** CC1=CC=CC=C1C(=O)N2CCC3=C2C=CC(=C3)C4=C(SC(=N4)NC(=O)CC5=CC6=C(C=C5)OCCO6)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the 2,3-dihydro-1-benzothiophene and the 2,3-dihydroindole moieties, contributes to the lipophilic character of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of smaller, more flexible segments, such as the indole and benzothiophene rings, could facilitate diffusion through the membrane.

3. **Polarity**: The molecule contains several polar functional groups, including the acetamide and the thiazole ring. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase and improve interaction with the polar head groups of the artificial membrane. However, the overall polar surface area is balanced by the lipophilic aromatic systems, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic systems not only contribute to lipophilicity but also may engage in π-π interactions with the lipid bilayer, enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall balance of hydrophilic and hydrophobic regions suggest that the molecule may have moderate hydration energy, which can influence its permeability.

8. **Membrane Affinity**: The given molecule appears to have a balanced affinity for both the aqueous and lipid phases, which is indicative of good permeability in the PAMPA assay.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 146

**SMILES:** C1=CC(=CC(=C1)C2=CN3C=NC=C3C(=C2)C4=CN=CC=C4)CO

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as pyridine and imidazo[1,2-a]pyridine, suggests a significant degree of lipophilicity. Aromatic rings are known to enhance lipophilicity, which generally increases permeability up to a certain threshold. However, the overall lipophilicity will depend on the balance with polar groups.

2. **Molecular Size and Weight**: The given molecule is relatively large, as indicated by its molecular weight of 336. This size can limit permeability due to steric hindrance and the difficulty in crossing the lipid bilayer. However, the specific arrangement of the rings and the presence of a phenyl group may help in optimizing the molecule's fit within the membrane.

3. **Polarity**: The molecule contains several nitrogen atoms within the pyridine and imidazo[1,2-a]pyridine rings, which contribute to its polar character. The polar surface area and the number of hydrogen bond donors/acceptors are relatively high, which may reduce permeability compared to non-polar molecules. However, the overall balance between polar and non-polar regions will determine the permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic systems can influence both lipophilicity and the ability to interact with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can impact its permeability. Lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and structural features suggests that while it may have some difficulty due to size and polar groups, its aromatic and rigid structure will support its permeation through the artificial membrane.

Final answer: Low-to-moderate permeability

------
# 147

**SMILES:** CC1=C(C=CC(=C1)SCC2=C(N=C(S2)C3=CC(=C(C=C3)C(F)(F)F)F)C)OCC(=O)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the difluorophenyl and trifluoromethylphenyl groups, contributes to the lipophilic nature of the molecule. These groups increase the overall hydrophobic character, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the artificial membrane.

3. **Polarity**: The molecule contains a hydroxyl group and ether linkages, which contribute to its polarity. However, the overall effect of these polar groups is mitigated by the strong lipophilic character imparted by the aromatic rings and trifluoromethyl group. The polar surface area and hydrogen bonding capacity are relatively low, which supports higher permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The thiazole ring introduces some rigidity to the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and potential entanglements with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and may also facilitate interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of fluorine atoms and trifluoromethyl group can lower the hydration energy of the molecule, making it easier to permeate the membrane by reducing the energy required to escape from the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic and rigid structural features, along with a balanced polarity, which collectively suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 148

**SMILES:** CC1=C(C(=CC=C1)CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC=CS3)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings and functional groups, which may contribute to a moderate molecular size. While larger molecules can have issues with permeability due to size constraints, the presence of aromatic rings and the sulfonamide group may help to balance this out.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic rings. The presence of a hydroxyl group also adds to the polarity, but the overall polar surface area is likely moderate.

4. **Charge**: The given molecule is neutral, which is typical for many drug molecules. This neutrality allows it to interact favorably with the lipid bilayer of the artificial membrane, enhancing its permeability.

5. **Rigidity**: The aromatic rings and the thiazole ring contribute to the rigidity of the molecule. Rigidity can help the molecule to maintain a conformation that is favorable for permeation through the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the hydroxyl and sulfonamide, may lead to moderate hydration energy. This can affect the molecule's ability to permeate the membrane, but the overall balance of lipophilicity and polarity suggests that the hydration energy is not a significant barrier.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is indicative of good membrane permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and structural features that favor membrane interaction.

Final answer: High permeability

------
# 149

**SMILES:** C1=CC(=CC(=C1)OC(F)(F)F)NC(=O)C2=CC(=NN2)C3=CC=CN3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the trifluoromethylphenoxy and pyrrole groups, contributes to the lipophilic nature of the molecule. The trifluoromethyl group is particularly lipophilic due to the electronegative fluorine atoms, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The overall molecular structure is relatively complex, with multiple rings and functional groups. While the aromatic rings and heterocycles contribute to a larger molecular size, the specific arrangement and connectivity may still allow for sufficient permeability, depending on the balance with other properties.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic and heterocyclic components, which are generally non-polar. However, the presence of a carboxamide group introduces some polarity, which can affect the molecule's solubility and interaction with the membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by maintaining a stable conformation that can interact effectively with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can facilitate interactions with the lipid bilayer through π-π stacking and hydrophobic interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of the trifluoromethyl group can lower the hydration energy of the molecule, making it easier for the molecule to traverse the aqueous environment surrounding the membrane and interact with the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests a moderate affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and balanced polarity.

Final answer: High permeability

------
# 150

**SMILES:** C1CCC(CC1)C(=O)NCCC2=NC3=CC=CC=C3N2CCO

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a member of benzimidazoles, which are known for their biological activity and ability to interact with various biological targets. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the benzimidazole moiety contributes to the lipophilic character of the molecule. Benzimidazole is a bicyclic structure that includes both a benzene ring and an imidazole ring, which can enhance lipophilicity. This suggests that the given molecule may have a moderate to high lipophilicity, which is generally favorable for permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple functional groups, including a carboxamide and a hydroxyethyl group. These groups can increase the molecular weight and size, which may reduce permeability. However, the benzimidazole core is relatively compact, which might mitigate this effect.

3. **Polarity**: The hydroxyethyl group introduces a polar character to the molecule, which can enhance solubility in aqueous environments. However, the overall polar surface area is balanced by the lipophilic benzimidazole and cyclohexane rings, suggesting moderate polarity. This balance can favor permeability.

4. **Charge**: The given molecule is neutral, which is generally favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The benzimidazole core provides a degree of rigidity to the molecule, which can facilitate passage through the membrane by reducing the flexibility and potential for entropic barriers.

6. **Aromaticity**: The benzene and imidazole rings contribute to the aromatic character, which can enhance lipophilicity and facilitate interactions with the lipid bilayer.

7. **Hydration Energy**: The presence of polar groups like the hydroxyethyl and carboxamide can lower the hydration energy, making the molecule more likely to permeate the membrane by overcoming the energy barrier associated with water molecules.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the given molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and structural features that facilitate membrane interaction.

Final answer: High permeability

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# 151

**SMILES:** COC1=CC=C(C=C1)NC2=NC(=NO2)C3=CC(=CC=C3)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of aromatic rings, specifically the methoxyphenyl groups, contributes to the molecule's lipophilicity. Aromatic rings are known to enhance lipophilicity, which can increase the molecule's ability to permeate through the lipid bilayer of the artificial membrane. This is because aromatic rings can engage in hydrophobic interactions with the lipid components of the membrane.

Secondly, the oxadiazole ring in the molecule is a heterocyclic structure that can contribute to the molecule's rigidity and planarity. This rigidity can facilitate the passage of the molecule through the membrane by reducing the energy required for conformational changes during permeation.

The methoxy groups attached to the phenyl rings introduce some degree of polarity, but their presence is balanced by the overall lipophilic nature of the aromatic systems. This balance can enhance the molecule's ability to interact with both the aqueous and lipid phases, potentially improving its permeability.

Additionally, the amine group in the oxadiazole ring can participate in hydrogen bonding, which may influence the molecule's interaction with the membrane. However, the presence of the methoxy groups may reduce the hydrogen bonding capacity, which can also contribute to higher permeability by reducing polar interactions with the aqueous environment.

Overall, the given molecule's combination of aromaticity, rigidity, and balanced polarity suggests that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 152

**SMILES:** C1CNCCC1C2=CC=C(C=C2)NS(=O)(=O)C3=CC=C(C=C3)NCC4=C(C(=CC=C4)Cl)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings can help to compact the structure, potentially mitigating this effect.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall structure is dominated by hydrophobic aromatic rings, suggesting a balance that might favor permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and potential entropic barriers.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The sulfonamide group and aromatic rings suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its interaction with the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, structural rigidity, and neutral charge.

Final answer: High permeability

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# 153

**SMILES:** CN1C(=NN=N1)SC2=NC=NC3=C2C(=CS3)Br

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a thienopyrimidine derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Thienopyrimidine Core**: This bicyclic structure combines a thiophene ring with a pyrimidine ring. The presence of these heterocycles can enhance lipophilicity, which generally increases permeability. The aromatic nature of these rings can also facilitate interactions with the lipid bilayer, potentially improving permeability.

2. **Bromo Substituent**: The bromine atom on the thienopyrimidine core adds to the lipophilicity of the molecule. Halogen atoms like bromine can enhance membrane permeability due to their ability to participate in halogen bonding and increase the overall hydrophobic character of the molecule.

3. **Tetrazole Ring**: The tetrazole moiety is known for its ability to mimic carboxylic acids, which can contribute to the molecule's overall polarity. However, in this context, the tetrazole ring is part of a larger structure that includes a sulfanyl linkage, which can modulate the overall polarity and lipophilicity balance.

4. **Sulfanyl Linkage**: The sulfanyl group connects the tetrazole ring to the thienopyrimidine core. Sulfur-containing linkages can influence the molecule's electronic properties and lipophilicity, potentially enhancing permeability by increasing the molecule's ability to interact with the lipid bilayer.

5. **Methyl Group**: The presence of a methyl group on the tetrazole ring can increase the lipophilicity of the molecule, which may further enhance its permeability.

Overall, the given molecule exhibits a combination of lipophilic and aromatic characteristics, along with specific functional groups that can interact with the lipid bilayer. These features suggest that the molecule would have high permeability in the PAMPA assay, as it is likely to efficiently traverse the artificial membrane.

Final answer: High permeability

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# 154

**SMILES:** CC#CC(=O)N1CCC[C@H]1C2=NC(=C3N2C=CN=C3N)C4=CC=C(C=C4)C(=O)NC5=CC=CC=N5

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex structure with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrrolo[2,1-a]phenazine core and the pyridine ring, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and a complex structure, which may limit its permeability due to size constraints. Larger molecules often have reduced permeability as they may face steric hindrance in passing through the artificial membrane.

3. **Polarity**: The molecule contains several polar groups, such as the amino group and the carbonyl group in the pyrrolo[2,1-a]phenazine moiety. These polar groups can form hydrogen bonds, which may enhance interactions with the aqueous phase and potentially reduce permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The presence of multiple aromatic rings and a rigid bicyclic system in the pyrrolo[2,1-a]phenazine core suggests a degree of rigidity. This rigidity can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure of the molecule may result in moderate hydration energy, which can influence its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity. However, its large size and complex structure may limit its permeability to some extent.

Final answer: Low-to-moderate permeability

------
# 155

**SMILES:** CC1=CN=C(C(=C1OC)C)CS(=O)C2=NC3=C(N2)C=CC(=N3)OC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of methoxy groups and a pyridine ring contribute to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a polar sulfinyl group and a pyridine ring, which can contribute to its overall polarity. However, the methoxy groups and the aromatic rings also provide significant lipophilic character, which may balance out the polarity and result in moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The presence of aromatic rings and a sulfinyl group can impart rigidity to the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings in the structure can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The presence of methoxy groups and the sulfinyl linkage may lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing the energy required to escape the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic groups suggests that the molecule has an affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilic and polar characteristics, along with the structural rigidity and aromaticity, supports this prediction.

Final answer: Low-to-moderate permeability

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# 156

**SMILES:** C1CN(CCC1C2=NOC3=C2C=CC(=C3)F)C(=O)C4CC(=O)N(C4)C5=NNC6=CC=CC=C65

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including the benzoxazole and indole moieties, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a limiting factor for permeability, the presence of multiple aromatic systems and a piperidine ring may allow for some flexibility and conformational adaptability, which can mitigate this effect to some extent.

3. **Polarity**: The molecule contains a fluorine atom and several nitrogen atoms, which contribute to its polarity. However, the overall polar surface area is relatively low due to the dominance of aromatic and hydrophobic regions. This balance suggests moderate polarity, which can facilitate membrane permeation.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without encountering steric hindrance from charged groups.

5. **Rigidity**: The aromatic systems, such as the benzoxazole and indole rings, contribute to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the given molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability. These interactions can stabilize the molecule within the membrane, facilitating its passage.

7. **Hydration Energy**: The presence of fluorine and nitrogen atoms may lower the hydration energy of the molecule, making it easier for the molecule to traverse the aqueous environment surrounding the membrane and interact with the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous phase and the lipid bilayer.

Overall, the given molecule exhibits a combination of lipophilicity, moderate polarity, and structural features that favor membrane permeability. These characteristics suggest that the molecule would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 157

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=CN=CC(=C2)C(=O)NC3=NC(=CS3)C4=CC=CC=C4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine groups, contributes to the lipophilic nature of the molecule. The sulfonamide group, while polar, is balanced by the lipophilic phenyl and pyridine rings, suggesting moderate lipophilicity.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings, which may limit its permeability due to size. However, the presence of aromatic rings can also enhance permeability by facilitating interactions with the lipid bilayer.

3. **Polarity**: The sulfonamide group introduces polar characteristics, but the overall structure is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can favor permeability.

4. **Charge**: The given molecule is neutral, which is typical for many drug molecules, allowing it to traverse lipid membranes more effectively than charged molecules.

5. **Rigidity**: The aromatic rings and heterocyclic structures contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and conformational changes.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl and pyridine groups, can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The balance of polar and nonpolar regions in the given molecule suggests that it may have moderate hydration energy, which can influence its permeability.

8. **Membrane Affinity**: The combination of lipophilic and polar groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for membrane permeability.

Overall, considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, rigidity, and polar characteristics that facilitate membrane interaction.

Final answer: Moderate permeability.

------
# 158

**SMILES:** CC1=C(C=C(C=C1)NC(=O)C2=C(C(=C(N2)C)C(=O)C)C)[S+](=O)(NC3=CC=C(C=C3)Br)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the acetylphenyl and pyrrole groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight due to its complex structure, which includes multiple aromatic rings and functional groups. While size can be a limiting factor for permeability, the presence of aromatic systems can help balance this by increasing lipophilicity.

3. **Polarity**: The molecule contains polar functional groups such as the acetyl group and the sulfonamide linkage. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase and affect membrane permeability. However, the overall low polar surface area due to the dominance of aromatic rings suggests moderate polarity, which can still allow for some permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and membrane affinity, which is beneficial for permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it may have moderate hydration energy, which can influence its interaction with the membrane and aqueous environment.

8. **Membrane Affinity**: The given molecule's structure suggests a balanced affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

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# 159

**SMILES:** C1CN(CCC1C(=O)N)C2=NC(=CS2)C3=CC=C(C=C3)OC4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenoxyphenyl group, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the specific arrangement of functional groups and rings might allow for sufficient permeation.

3. **Polarity**: The molecule contains a phenoxy group, which introduces some degree of polarity. However, the overall structure is dominated by aromatic and hydrocarbon components, suggesting a balance that might favor permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced diffusion through lipid membranes.

5. **Rigidity**: The thiazole ring and aromatic systems contribute to the rigidity of the molecule. This rigidity can enhance its ability to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The presence of multiple aromatic rings can increase lipophilicity and facilitate interactions with the lipid membrane, enhancing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests it has a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, neutral charge, and structural rigidity, which facilitate its interaction with the artificial membrane.

Final answer: High permeability

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# 160

**SMILES:** CC1=C(C2=C(N1C3=CC=CC=C3)C=CC(=C2)O)C(=O)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of indole, which is a bicyclic structure consisting of a benzene ring fused to a pyrrole ring. This core structure is known for its aromaticity, which can influence the molecule's interaction with the lipid bilayer in the PAMPA assay.

The presence of a hydroxy group on the indole ring increases the molecule's polarity, which can enhance hydrogen bonding with the membrane and potentially improve permeability. However, the hydroxy group also contributes to the polar surface area, which may limit permeability due to increased solubility in aqueous environments.

The methyl group on the indole ring adds to the lipophilicity of the molecule, which generally enhances permeability by increasing the molecule's ability to interact with the hydrophobic lipid bilayer.

The phenyl group attached to the indole structure further increases the lipophilicity and aromatic character of the molecule. Aromatic rings can facilitate interactions with the lipid bilayer through π-π stacking and van der Waals forces, which can enhance permeability.

The ethanone group at the end of the molecule introduces a carbonyl group, which can participate in hydrogen bonding and may slightly reduce permeability due to its polar nature. However, the overall effect of this group is likely minimal compared to the other structural features.

Overall, the given molecule exhibits a balance of lipophilic and polar characteristics, with a significant aromatic component. These features suggest that the molecule would have high permeability in the PAMPA assay, as it can effectively interact with the lipid bilayer while maintaining sufficient solubility in the aqueous phase.

Final answer: High permeability

------
# 161

**SMILES:** CC1=CC(=NC(=C1)NC(=S)N2CCN(CC2)C3=CC(=CC=C3)[N+](=O)[O-])C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of dimethyl groups on the pyridine ring increases the lipophilicity of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of a piperazine ring can help to reduce steric effects by providing flexibility.

3. **Polarity**: The molecule contains a carbothioamide group, which introduces some polarity. However, the overall polarity is balanced by the lipophilic pyridine and dimethyl groups, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced diffusion through lipid membranes.

5. **Rigidity**: The aromatic pyridine and nitropyridine rings contribute to the rigidity of the molecule. This rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the carbothioamide and nitro groups may lead to moderate hydration energy, which can affect membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a balanced molecular size, and structural features that favor membrane permeability. Therefore, it is likely to have high permeability in the PAMPA assay.

Final answer: High permeability

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# 162

**SMILES:** C1CC2=C(C(N=C(N2)NC3=NC4=C(O3)C=CC(=C4)F)C5=C(C=NN5)Cl)C(=O)C1

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chloro-substituted pyrimidine and the quinazoline moiety, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a limiting factor for permeability, the presence of multiple rings and heteroatoms may allow for some flexibility and conformational adaptability, which can mitigate this effect to some extent.

3. **Polarity**: The molecule contains several polar functional groups, including the oxadiazole ring and the quinazoline moiety. However, the overall polar surface area is relatively low due to the dominance of aromatic and heterocyclic structures, which are generally non-polar. This suggests that the molecule may have moderate polarity, which can influence its permeability.

4. **Charge**: The given molecule is neutral, which is typical for many bioactive compounds. This neutrality allows it to interact favorably with the lipid bilayer, enhancing its permeability.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings contributes to the rigidity of the molecule. While rigidity can sometimes hinder permeability due to limited conformational flexibility, in this case, it may also facilitate interactions with the membrane.

6. **Aromaticity**: The aromatic systems present in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure of the molecule suggest that it may have moderate hydration energy. This can influence its solubility and permeability, with lower hydration energy generally favoring better membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, balanced polarity, and favorable interactions with the lipid bilayer.

Final answer: High permeability

------
# 163

**SMILES:** C1CC(=O)NC2=CC(=C(C=C21)S(=O)(=O)NC3=CC(=C(C=C3)F)Cl)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a quinoline derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the quinoline core and the phenyl group, contributes to the lipophilicity of the molecule. The chloro and fluoro substituents on the phenyl ring further enhance lipophilicity due to their electron-withdrawing nature, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The quinoline core and the attached functional groups suggest a moderate molecular size. While the molecule is not extremely large, its size is sufficient to interact with the artificial membrane, potentially allowing for moderate permeability.

3. **Polarity**: The sulfonamide group introduces a polar character to the molecule, which can affect its solubility and permeability. However, the overall balance of lipophilic and polar groups suggests that the molecule may still exhibit moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without being repelled by charges.

5. **Rigidity**: The quinoline core provides a degree of rigidity, which can facilitate passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The aromatic systems in the molecule can enhance its ability to interact with the lipid bilayer through π-π interactions, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups like the sulfonamide and the fluorine atoms may reduce the hydration energy, aiding in membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable membrane affinity, which can contribute to its permeability.

Overall, the given molecule's structural features suggest that it would exhibit moderate to high permeability in the PAMPA assay, balancing lipophilicity with polar functional groups to interact effectively with the artificial membrane.

Final answer: Moderate permeability.

------
# 164

**SMILES:** CCCCCN1C(=O)C2=C(C=C(C=C2)C(=O)NCCCN3CCC(CC3)C)NC1=O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinazoline derivative with several functional groups and structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the quinazoline core and the alkyl chains, such as the butyl and methylpropyl groups, contribute to the lipophilic nature of the molecule. This suggests that the molecule is likely to have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The overall molecular structure, including the quinazoline core and the attached functional groups, results in a relatively large molecular size. While size is a factor in permeability, the presence of multiple functional groups and the quinazoline core may still allow for sufficient permeability, but it might be limited compared to smaller molecules.

3. **Polarity**: The molecule has a low polar surface area due to the absence of multiple polar functional groups. The presence of a carboxamide group and the quinazoline nitrogen atoms contribute to some degree of polarity, but overall, the molecule is likely to have a low polar surface area, which is favorable for permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to permeate lipid membranes.

5. **Rigidity**: The quinazoline core provides a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent conformation.

6. **Aromaticity**: The quinazoline ring system is aromatic, which can enhance lipophilicity and influence interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable membrane affinity, which is beneficial for permeability.

Overall, the given molecule is expected to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and favorable structural characteristics.

Final answer: High permeability

------
# 165

**SMILES:** COC1=CC=CC=C1S(=O)(=O)NC2=C(C=CN=C2)C(=O)NC3=NC(=CS3)C4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridinyl groups, contributes to the lipophilic nature of the molecule. The methoxy group on the phenyl ring also increases lipophilicity, which generally enhances membrane permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and heteroatoms. While the size of the molecule is moderate, the presence of these rings can still allow for sufficient permeability, but it may be limited by steric hindrance.

3. **Polarity**: The sulfonamide group introduces some polarity, but the overall structure is dominated by the lipophilic aromatic rings. The low polar surface area and the presence of hydrogen bond donors and acceptors suggest moderate polarity, which can influence permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without encountering electrostatic barriers.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The aromatic rings, including the phenyl and pyridinyl groups, can interact with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide, may lead to moderate hydration energy, which can affect the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 166

**SMILES:** C1=CC(=C(C=C1Cl)C2=NC3=NC=CN=C3C(=N2)NC4=CC=NC=C4)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a pyrimidine derivative with several functional groups and structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and phenyl groups, contributes to the lipophilic nature of the molecule. The chloro and fluoro substituents on the phenyl ring further enhance lipophilicity, as halogens increase the molecule's hydrophobic character. This suggests that the molecule is likely to have high permeability due to its ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively small, which is beneficial for permeability. Smaller molecules generally have higher permeability as they can more easily traverse the membrane without significant steric hindrance.

3. **Polarity**: The pyridine rings introduce some degree of polarity, but the overall structure is dominated by the lipophilic aromatic systems. The low polar surface area and the presence of hydrogen bond acceptors (nitrogen atoms) suggest that the molecule has moderate polarity, which is balanced by its lipophilic characteristics, contributing to its permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability. Charged molecules often have reduced permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The pyrimidine and pyridine rings contribute to the rigidity of the molecule. This rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation while interacting with the membrane.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The presence of halogens and aromatic systems suggests that the hydration energy of the molecule is relatively low, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule exhibits properties that are generally associated with high permeability in the PAMPA assay, such as high lipophilicity, moderate polarity, neutral charge, and structural rigidity.

Final answer: High permeability

------
# 167

**SMILES:** CC1(CNC2=C1C=CC(=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the indole and pyridine moieties, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 342.3 g/mol. While size is a limiting factor for permeability, the presence of aromatic rings and the indole moiety may help to maintain some degree of permeability due to their planar structure.

3. **Polarity**: The molecule has a low polar surface area, which is a result of the aromatic rings and the absence of highly polar functional groups. This contributes to its ability to permeate the membrane, as it can interact favorably with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indole and pyridine rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The aromatic nature of the indole and pyridine rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, promoting permeability.

7. **Hydration Energy**: The molecule's hydration energy is likely lower due to its aromatic and non-polar characteristics, which can enhance its ability to permeate the membrane by reducing its affinity for water.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic, aromatic, and rigid characteristics that contribute to its ability to permeate the artificial membrane, resulting in a classification of high permeability in the PAMPA assay.

Final answer: High permeability

------
# 168

**SMILES:** COC1=CC=C(C=C1)N2C(=O)NC(=N2)C3CCN(CC3)[S+](=O)(C4=CC=CC(=C4)C(F)(F)F)[O-]

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the methoxyphenyl and trifluoromethylphenyl groups, contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The methoxy group and the trifluoromethyl group contribute to the molecule's polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, which may allow the molecule to maintain a moderate level of permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The triazole ring introduces a degree of rigidity to the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by providing a stable conformation that can interact effectively with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may further enhance permeability.

7. **Hydration Energy**: The presence of the trifluoromethyl group can lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing its affinity for water.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilic and polar features, along with the structural rigidity and aromaticity, suggests that it can interact effectively with the artificial membrane, but the large and complex structure may limit its permeability to some extent.

Final answer: Low-to-moderate permeability

------
# 169

**SMILES:** CC1CCCCN1C2=NC=NC(=C2[N+](=O)[O-])N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a pyrimidine derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a nitro group on the pyrimidine ring contributes to the molecule's lipophilicity. Nitro groups are electron-withdrawing, which can enhance the molecule's ability to interact with the lipid membrane, potentially increasing permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively small, which is beneficial for permeability. The pyrimidine core and the piperidine ring contribute to a compact molecular framework, facilitating diffusion through the membrane.

3. **Polarity**: The pyrimidine ring and the piperidine moiety introduce some degree of polarity. However, the nitro group and the amine group on the pyrimidine ring balance this by increasing lipophilicity. The overall polar surface area and hydrogen bonding capacity suggest moderate polarity, which may not hinder permeability significantly.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without encountering electrostatic barriers.

5. **Rigidity**: The aromatic pyrimidine ring provides some rigidity, which can aid in membrane permeation by maintaining a stable conformation as the molecule interacts with the membrane.

6. **Aromaticity**: The pyrimidine ring contributes to the molecule's aromatic character, which can enhance lipophilicity and facilitate interactions with the lipid bilayer.

7. **Hydration Energy**: The presence of the nitro group and the amine group may lower the hydration energy of the molecule, making it easier for the molecule to penetrate the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests it has a favorable membrane affinity, which is conducive to high permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, and structural features that facilitate membrane interaction.

Final answer: High permeability

------
# 170

**SMILES:** CC1=CC(=NC(=C1)NC(=S)N2CCN(CC2)C3=C(C=C(C=C3)Cl)[N+](=O)[O-])C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of chloro and nitro groups on the aromatic ring increases the lipophilicity of the molecule. These groups are electron-withdrawing, which can enhance the molecule's ability to interact with the lipid membrane, potentially increasing permeability.

2. **Molecular Size and Weight**: The molecule contains a piperazine ring, which is a relatively small heterocyclic amine. The overall molecular size is moderate, and the presence of aromatic and heterocyclic rings contributes to a balance between hydrophilic and lipophilic properties, which can favor permeability.

3. **Polarity**: The molecule has a polar surface area due to the nitro and chloro groups, as well as the carbothioamide group. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity. The presence of a low number of hydrogen bond donors and acceptors (such as the thioamide group) may also contribute to higher permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the piperazine ring contribute to a degree of rigidity, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups like the nitro and thioamide groups may reduce the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic groups suggests that the molecule has an affinity for both the aqueous and lipid phases, which is favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a moderate molecular size, and a balanced affinity for the membrane, suggesting that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 171

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=CC=CC(=C2Cl)C(=O)NC3=NC(=CS3)C4=CC=CC=C4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of a chlorophenyl group and a thiazole ring suggests that the molecule is relatively lipophilic. These aromatic and heterocyclic components contribute to the molecule's ability to interact with lipid membranes, enhancing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.4 g/mol. While size is a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help to maintain a balance between size and permeability.

3. **Polarity**: The sulfonamide group introduces some polarity, but the overall structure is dominated by the lipophilic aromatic and heterocyclic components. The presence of a polar sulfonamide group can also facilitate hydrogen bonding, which may aid in membrane interaction.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without being repelled by a charge.

5. **Rigidity**: The aromatic rings and the thiazole ring contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by reducing the flexibility of the molecule, which can otherwise hinder passage through the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the structure can interact with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of both hydrophobic and hydrophilic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

8. **Membrane Affinity**: The combination of lipophilic and polar groups suggests that the given molecule has a balanced membrane affinity, which is conducive to high permeability in the PAMPA assay.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

------
# 172

**SMILES:** COC1=CC=CC(=C1O)CNC2=CC=C(C=C2)S(=O)(=O)NC3=CN=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridinyl groups, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and functional groups. While the aromatic rings can increase lipophilicity, the overall size and weight may limit permeability due to steric hindrance and potential difficulty in crossing the membrane.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the presence of methoxy and hydroxy groups also contributes to the polarity, potentially balancing the lipophilic aromatic rings.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The aromatic rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent shape that can interact favorably with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its ability to interact with the lipid bilayer through π-π interactions, potentially increasing permeability.

7. **Hydration Energy**: The presence of polar groups like the hydroxy and sulfonamide groups may reduce the hydration energy, aiding in membrane permeation.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic groups suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, neutral charge, and structural features that facilitate membrane interaction.

Final answer: High permeability

------
# 173

**SMILES:** CC1=C(N(C(=C1C(=O)C)C)C)C(=O)NC2=CC(=CC=C2)[S+](=O)(N(C)C)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of multiple methyl groups and an acetyl group on the pyrrole ring increases the lipophilicity of the molecule. This suggests that the molecule may have a higher permeability due to its ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively small, which is beneficial for permeability as smaller molecules can more easily traverse the membrane.

3. **Polarity**: The amide group and the sulfonamide moiety contribute to the polarity of the molecule. However, the overall structure is balanced by the lipophilic methyl and acetyl groups, which may allow the molecule to maintain a moderate level of permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the pyrrole core provide a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups like the sulfonamide and amide may reduce the hydration energy, which can improve membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the molecule has an affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Overall, the given molecule's structural features, such as its lipophilicity, moderate polarity, and balanced hydrophilic-hydrophobic nature, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 174

**SMILES:** CCC1=C(C=C(C=C1)NC(=O)C2=C(C(=C(N2)C)C(=O)C)C)[S+](=O)(NC3=CC=C(C=C3)C#N)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the acetylphenyl and pyrrole groups, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight due to its complex structure, which includes multiple aromatic rings and functional groups. This size can potentially limit its permeability, as larger molecules may have difficulty passing through the artificial membrane.

3. **Polarity**: The molecule contains polar functional groups such as the sulfonylamino and amide groups. These groups can increase the polarity of the molecule, which may reduce its permeability. However, the overall balance between lipophilic and polar components will determine the net effect on permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings and the pyrrole moiety contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings in the molecule can interact with the lipid bilayer through π-π interactions, potentially enhancing its permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have a moderate hydration energy, which can influence its permeability. Lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 175

**SMILES:** COC1=CC2=C(C=C1)OC(=N2)NC3=NC(C4=C(N3)CCCC4=O)C5=C(C=NN5)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including the chloro-substituted benzoxazole and the pyrimidine ring, suggests a significant degree of lipophilicity. This is likely to enhance the molecule's ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and rings. While size can be a limiting factor for permeability, the presence of aromatic systems and heteroatoms may facilitate interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule contains several polar groups, such as the chloro substituent and the oxazole nitrogen, which can contribute to hydrogen bonding and dipole interactions. However, the overall polarity is balanced by the extensive aromatic system, which may reduce the polar surface area and enhance lipophilicity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles contributes to a rigid structure, which can facilitate passage through the membrane by reducing the number of conformational changes required.

6. **Aromaticity**: The aromatic systems, including the benzoxazole and pyrimidine rings, can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable structural rigidity and aromaticity.

Final answer: High permeability

------
# 176

**SMILES:** CC1=C(C=C(C=C1)NC(=O)NCC2CCN(CC2)CC3=CC(=CC=C3)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to the permeability characteristics mentioned earlier.

1. **Lipophilicity**: The given molecule contains aromatic rings, specifically chlorophenyl groups, which contribute to its lipophilic nature. The presence of chlorine atoms on these phenyl rings can enhance lipophilicity due to the electron-withdrawing effect, which increases the molecule's hydrophobic character. This suggests that the molecule may have high permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a piperidine moiety. While the aromatic rings and the piperidine ring contribute to the overall molecular size, the presence of these groups also suggests a degree of rigidity, which can favor permeability due to better alignment and interaction with the lipid bilayer.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the lack of multiple polar functional groups. The presence of chloro substituents and the urea linkage contribute to a balance between hydrophobic and hydrophilic interactions, which is favorable for membrane permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The aromatic rings and the piperidine moiety contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can influence the molecule's interaction with the lipid bilayer, potentially enhancing its permeability through π-π interactions with the aromatic residues of the membrane.

7. **Hydration Energy**: The given molecule likely has a lower hydration energy due to its hydrophobic character, which facilitates its passage through the lipid bilayer by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests that it has a favorable membrane affinity, which is essential for high permeability in PAMPA.

Considering these factors, the given molecule is likely to exhibit high permeability in the Parallel Artificial Membrane Permeability Assay.

Final answer: High permeability

------
# 177

**SMILES:** CC1=CC(=C(N1C2=CC=NC=C2)C)C3=NN=C4N3CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methyl groups and the pyridine rings contribute to the lipophilic nature of the molecule. This suggests that the molecule may have a relatively high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of multiple rings and heteroatoms may create a balance that allows for sufficient permeability, but not excessively so.

3. **Polarity**: The pyridine rings introduce some degree of polarity, but the overall structure is dominated by non-polar hydrocarbon chains and rings. The low polar surface area and the presence of hydrogen bond acceptors (pyridine nitrogen atoms) suggest that the molecule may have moderate polarity, which can influence its interaction with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple fused rings, including the pyridine and triazatricyclic systems, contributes to a rigid structure. This rigidity can enhance the ability of the molecule to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The pyridine rings contribute to the aromatic character of the molecule, which can influence its interaction with the lipid bilayer through π-π interactions and hydrophobic effects.

7. **Hydration Energy**: The presence of nitrogen atoms in the pyridine and triazatricyclic rings may lower the hydration energy of the molecule, facilitating its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay, owing to its lipophilicity, moderate polarity, neutral charge, and rigid, aromatic structure.

Final answer: High permeability

------
# 178

**SMILES:** CC[S+](=O)(NC1=CC=CC=C1C(=O)NC2=NC(=CS2)C3=CC=CC=C3)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a benzamide derivative, which suggests it has a benzene ring attached to an amide group. This structural feature can contribute to its lipophilicity, enhancing its ability to permeate lipid membranes. The presence of the phenyl group further increases its hydrophobic character, which is beneficial for membrane permeability.

The thiazole ring in the molecule introduces a heterocyclic component, which can influence its electronic properties and potentially its interaction with the membrane. Thiazole rings are known for their aromaticity, which can stabilize the molecule and facilitate its passage through the membrane.

The ethylsulfonylamino group is a polar moiety that can increase the molecule's solubility in water, potentially improving its ability to interact with the aqueous environment surrounding the membrane. However, the overall effect on permeability will depend on the balance between the polar and non-polar regions of the molecule.

Considering these structural features, the given molecule is likely to exhibit high permeability due to its combination of lipophilic aromatic rings and polar functional groups, which together promote interaction with the lipid bilayer of the artificial membrane.

Final answer: High permeability

------
# 179

**SMILES:** C1=CC=C2C(=C1)/C(=C\C3=CC=C(C=C3)O)/C(=O)N2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a hydroxycoumarin derivative, which suggests that it has a coumarin core structure with a hydroxyl group attached to a phenyl ring. This structural feature is significant in determining its permeability.

1. **Lipophilicity**: The presence of the coumarin core, which is a fused aromatic system, contributes to the lipophilicity of the molecule. This aromatic system can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Polarity**: The hydroxyl group on the phenyl ring introduces some polarity to the molecule. However, the overall structure is dominated by the lipophilic coumarin core, which may outweigh the polar effects, leading to moderate lipophilicity.

3. **Molecular Size and Weight**: The given molecule is relatively small, which can facilitate its passage through the artificial membrane. Smaller molecules generally have higher permeability due to less steric hindrance.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers.

5. **Rigidity**: The aromatic rings in the coumarin structure contribute to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can also influence the molecule's interaction with the membrane, potentially enhancing its permeability through π-π interactions with the lipid bilayer.

7. **Hydration Energy**: The hydroxyl group can form hydrogen bonds, which may affect the hydration energy of the molecule. However, the overall effect on permeability will depend on the balance between the hydrophilic and hydrophobic interactions.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic properties in the given molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 180

**SMILES:** C1CC2=C(C(N=C(N2)NC3=NC4=CC=CC=C4O3)C5=C(C=NN5)Cl)C(=O)C1

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chloro-substituted benzoxazole and the pyrimidine ring, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 344.3 g/mol. While size is a limiting factor for permeability, the presence of multiple rings and heteroatoms may allow for some flexibility and conformational adaptability, which can mitigate this effect to some extent.

3. **Polarity**: The molecule contains several polar functional groups, including the oxazole and pyrimidine rings, as well as a carbonyl group. However, the overall polar surface area is relatively low due to the dominance of aromatic and heterocyclic structures, which are generally non-polar. This suggests that the molecule may have a moderate polar surface area, which could impact its permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to traverse lipid membranes.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings contributes to the rigidity of the molecule. While rigidity can sometimes hinder permeability due to limited conformational flexibility, the specific arrangement of these rings may allow for sufficient adaptability to interact with the membrane.

6. **Aromaticity**: The aromatic systems present in the molecule can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure of the molecule suggest that it may have a moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a favorable membrane affinity, which is essential for permeability in the PAMPA assay.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate polar surface area, and balanced affinity for both aqueous and lipid environments.

Final answer: High permeability

------
# 181

**SMILES:** CC1=C(C=C(C=C1)C(=O)NC2=CC3=C(C=C2)OC(=N3)C4=CN=CC=C4)[N+](=O)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzamide and benzoxazole moieties, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 344.35 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may allow for some flexibility and conformational adaptability, which can mitigate the negative effects of size.

3. **Polarity**: The molecule contains a nitro group, which is polar, and a pyridine ring, which also contributes to polarity. However, the overall polar surface area is relatively low due to the dominance of aromatic and heterocyclic structures, which are non-polar. This suggests that the molecule may have moderate polarity, which can affect its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles contributes to a degree of rigidity. While rigidity can sometimes hinder permeability due to limited conformational flexibility, the specific arrangement of these rings may allow for sufficient adaptability to traverse the membrane.

6. **Aromaticity**: The aromatic rings, including the benzamide and benzoxazole, can interact with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure, with its aromatic and heterocyclic components, likely has a lower hydration energy, which can facilitate membrane permeation by reducing the energy required to escape the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate polarity, neutral charge, and balanced membrane affinity.

Final answer: High permeability

------
# 182

**SMILES:** CN(C1=CC=CC=C1)C(=O)CSC2=NC3=C(CCCC3)C(=O)N2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a phenyl group and a quinazolinyl moiety contributes to the lipophilic nature of the molecule. These aromatic rings increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and a moderate molecular weight. While size can be a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help in maintaining a balance, allowing some degree of permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar aromatic rings and a quinazolinyl group. Additionally, the N-methylacetamide moiety contributes to the overall polarity, but the balance between hydrophobic and hydrophilic regions is crucial. The low polar surface area suggests that the molecule might have moderate to high permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The quinazolinyl and phenyl rings introduce rigidity to the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also play a role in π-π interactions with the lipid bilayer, potentially aiding in membrane permeation.

7. **Hydration Energy**: The presence of a sulfur atom in the thioether linkage and the overall structure suggest that the molecule has a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, allowing it to interact with both the aqueous and lipid phases of the membrane.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate size, neutral charge, and favorable balance of hydrophobic and hydrophilic interactions.

Final answer: High permeability

------
# 183

**SMILES:** CN1C2=C(C=CC(=C2)C(=O)NCC3=CC=C(C=C3)Br)[S@@](=O)C4=CC=CC=C4C1=O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the 4-bromophenyl group and the benzo[b][1,4]benzothiazine core, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and a complex structure, which may limit its permeability due to size constraints. Larger molecules often have reduced permeability because they may have difficulty traversing the lipid bilayer.

3. **Polarity**: The molecule contains a carboxamide group, which can contribute to polarity. However, the overall structure is dominated by aromatic and lipophilic components, suggesting that the polar surface area is not high enough to significantly limit permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a bicyclic system contributes to the rigidity of the molecule. Rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of a sulfone group (1,1-dioxo) suggests that the molecule may have a lower hydration energy, which can improve its ability to permeate the membrane by reducing its affinity for water.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

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# 184

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=CC(=C2)C(=O)NC3=NC(=CS3)C4=CC=CC=C4)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and methoxyphenyl groups, contributes to the lipophilic nature of the molecule. The methoxy group also adds to this lipophilicity due to its electron-donating properties, which can enhance the molecule's ability to interact with the lipid components of the membrane.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple aromatic rings and heterocyclic components. While these features can contribute to a larger molecular weight, the specific arrangement and connectivity of these rings may still allow for sufficient permeability, depending on the overall size and shape.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall balance of lipophilic and polar groups suggests that the molecule may still exhibit moderate permeability.

4. **Charge**: The given molecule is neutral, which is typical for many sulfonamides. This neutrality allows it to traverse the lipid bilayer more effectively compared to charged molecules.

5. **Rigidity**: The aromatic rings and the thiazole moiety contribute to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The presence of multiple aromatic systems can influence the molecule's interaction with the lipid bilayer, potentially enhancing its permeability through hydrophobic interactions.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it may have a moderate hydration energy, which can influence its permeability.

8. **Membrane Affinity**: The combination of lipophilic and polar groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for membrane permeability.

Considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, rigidity, and a suitable molecular size for membrane passage.

Final answer: High permeability

------
# 185

**SMILES:** C1=CC=C2C(=C1)C(=NC(=N2)C3=CC=NC=C3)NC4=CC=NN4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the pyridine and quinazoline rings, suggests that the given molecule is likely to be lipophilic. This lipophilicity can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 342.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may allow for some degree of flexibility, which can mitigate the negative effects of size.

3. **Polarity**: The pyridine and pyrazine rings introduce some degree of polarity to the molecule. However, the overall structure is dominated by aromatic systems, which are generally non-polar. The low polar surface area and the presence of only a few hydrogen bond donors/acceptors suggest that the given molecule may have moderate polarity, which could influence its permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to a relatively rigid structure, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic nature of the pyridine and quinazoline rings can enhance lipophilicity and may also facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of multiple nitrogen atoms in the heterocycles may lead to moderate hydration energy, which can influence the molecule's ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it may have a favorable membrane affinity, aiding in its permeability.

Overall, the given molecule's combination of lipophilicity, aromaticity, and moderate polarity suggests that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 186

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=CN=C2)C(=O)NC3=NC(=CS3)C4=CC=CC=C4Cl

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the chlorophenyl and pyridine groups, contributes to the lipophilic nature of the molecule. The sulfonamide group, while polar, is balanced by the lipophilic aromatic systems, suggesting moderate lipophilicity.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and heterocycles. This complexity may limit its permeability due to steric hindrance, but the presence of smaller functional groups like the sulfonamide and thiazole may still allow for some degree of permeability.

3. **Polarity**: The sulfonamide group introduces some polarity, but the overall structure is dominated by aromatic and heterocyclic components, which are less polar. This suggests that the molecule may have moderate permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without encountering electrostatic barriers.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and conformational changes.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The balance of polar and nonpolar regions in the molecule suggests that it may have moderate hydration energy, which can influence its permeability.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both aqueous and lipid environments, which is typical for compounds with moderate lipophilicity and polarity.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilic and polar features, along with its structural rigidity and aromaticity, suggests that it can interact effectively with the artificial membrane, but may not have the highest permeability due to its size and complexity.

Final answer: Low-to-moderate permeability

------
# 187

**SMILES:** C1=CC(=C(C=C1NC2=NC(=NC=C2)C3=CC=NC=C3)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and difluorophenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule contains multiple heterocyclic rings, which can increase its molecular size and weight. While larger molecules generally have lower permeability due to size constraints, the specific arrangement of these rings may allow for sufficient flexibility and conformational adaptability to traverse the membrane.

3. **Polarity**: The pyridine rings introduce nitrogen atoms, which can contribute to the overall polarity of the molecule. However, the difluorophenyl group and the aromatic nature of the compound may counterbalance this, resulting in a moderate polarity. The presence of nitrogen atoms also suggests potential hydrogen bonding capabilities, which can influence interactions with the membrane.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The heterocyclic structure, particularly the pyridine rings, imparts a degree of rigidity to the molecule. This rigidity can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic nature of the difluorophenyl and pyridine rings can enhance lipophilicity and influence the molecule's ability to insert into the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups and aromatic systems suggests that the hydration energy of the given molecule may be moderate, allowing it to interact with both the aqueous environment and the lipid membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions, due to the aromatic and nitrogen-containing groups, suggests that the given molecule has a balanced affinity for both phases, which is beneficial for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular flexibility, and membrane affinity.

Final answer: High permeability

------
# 188

**SMILES:** C1CC(C2=C(C1)C3=C(N2)C(=CC=C3)Cl)NC(=O)C4=CC5=C(C=C4)OCO5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a benzodioxole moiety, which is a methylenedioxyphenyl group, contributes to the lipophilic nature of the molecule. This group is known for enhancing lipophilicity, which can increase membrane permeability up to a certain point.

2. **Molecular Size and Weight**: The tetrahydro-1H-carbazole portion of the molecule is relatively large and rigid. This rigidity can help the molecule maintain a stable conformation as it interacts with the membrane, potentially aiding in permeability. However, the overall size and weight of the molecule may limit its permeability due to steric hindrance.

3. **Polarity**: The molecule contains a carboxamide group, which introduces some polarity. However, the overall polar surface area is relatively low due to the presence of the aromatic rings, which dominate the structure. This suggests that the molecule may have moderate polarity, which can affect its permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Aromaticity**: The aromatic rings present in the structure can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

6. **Hydration Energy**: The presence of the carboxamide group may contribute to some degree of hydration energy, but the overall structure is likely to have low hydration energy due to the dominance of hydrophobic aromatic rings.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for membrane permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable interactions with the lipid bilayer.

Final answer: High permeability

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# 189

**SMILES:** COC1=CC(=CC(=C1OC)OC)NC(=O)C2=CC(=NO2)C3=CC=CC=C3O

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of a hydroxyphenyl group contributes to the molecule's polarity, which can enhance its solubility in aqueous environments. However, the hydroxy group also increases the polar surface area, which may reduce permeability due to interactions with the aqueous phase. 

The methoxy groups on the phenyl ring increase the lipophilicity of the molecule, which generally enhances permeability by facilitating passage through the lipid bilayer. These groups can also contribute to the molecule's ability to interact with the lipid membrane through van der Waals forces.

The isoxazole ring is a heterocyclic structure that can contribute to the molecule's rigidity and planarity. This rigidity can improve permeability by allowing the molecule to fit more easily into the lipid bilayer. The presence of nitrogen and oxygen in the isoxazole ring can also influence the molecule's electronic properties, potentially affecting its interaction with the membrane.

The carboxamide group is polar and can form hydrogen bonds, which may reduce permeability by interacting with the aqueous environment. However, it can also contribute to the molecule's overall stability and solubility profile.

Overall, the given molecule's combination of lipophilic methoxy groups, polar hydroxy and carboxamide groups, and a rigid isoxazole ring suggests that it may have moderate permeability in the PAMPA assay. The balance of these features allows the molecule to interact with both the aqueous and lipid phases, potentially facilitating its passage through the artificial membrane.

Final answer: Low-to-moderate permeability.

------
# 190

**SMILES:** CC1=CC(=NO1)NS(=O)(=O)C2=CC=C(C=C2)NCCC3=CC(=C(C=C3)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the 3,4-dichlorophenyl group contributes to the lipophilic nature of the molecule. Chlorine atoms increase the electron-withdrawing capacity, enhancing the molecule's lipophilicity. This generally increases permeability up to a certain threshold, but the overall effect depends on the balance with other polar groups.

2. **Molecular Size and Weight**: The molecule is relatively small, which typically correlates with higher permeability. The ethyl linkage and the sulfonamide group contribute to this small size, allowing the molecule to traverse the membrane more easily.

3. **Polarity**: The sulfonamide group introduces some polarity, which can affect the balance between hydrophilicity and lipophilicity. However, the dichlorophenyl group and the aromatic ring system contribute to the overall lipophilicity, potentially offsetting the polar effects.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged species often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings and the oxazole ring contribute to a degree of rigidity, which can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the oxazole ring and the sulfonamide group may lower the hydration energy, facilitating membrane permeation.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 191

**SMILES:** CC1=CN=C(N=C1NCC2=CC=C(C=C2)C3=CN=CC=C3)C4=CC=CC=C4C5COC5

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrimidine and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule contains multiple rings, including a pyrimidine and a pyridine, which contribute to its overall size and weight. While larger molecules can have reduced permeability due to size constraints, the specific arrangement and connectivity of these rings may still allow for sufficient permeation.

3. **Polarity**: The pyridine and pyrimidine rings introduce some degree of polarity, but the overall structure is dominated by aromatic and hydrocarbon components, which suggest a relatively low polar surface area. This could favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a saturated oxetane ring contributes to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Hydration Energy**: The oxetane ring, a four-membered ether, may contribute to a lower hydration energy, which can facilitate membrane permeation by reducing the energy required to transition from an aqueous to a lipid environment.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Overall, the given molecule's structural features, including its lipophilicity, rigidity, and balanced polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 192

**SMILES:** CC1=C(C=C(C=C1)NC2=NC(=NC3=CC=CC=C32)C4=CC=NC=C4)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinazoline derivative with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the quinazoline core and the pyridine ring, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively small, which is beneficial for permeability. Smaller molecules generally have higher permeability due to less steric hindrance and better fit within the membrane pores.

3. **Polarity**: The molecule contains a fluorine atom attached to a methyl group, which can increase lipophilicity while maintaining a balance with the polar pyridine and amine groups. The low polar surface area and the presence of hydrogen bond donors/acceptors suggest moderate polarity, which can facilitate membrane permeation.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The quinazoline and pyridine rings contribute to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic nature of the quinazoline and pyridine rings can influence the molecule's interaction with the membrane, potentially enhancing lipophilicity and membrane affinity.

7. **Hydration Energy**: The presence of polar groups, such as the amine and pyridine nitrogen, may lead to moderate hydration energy, which can affect the molecule's solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a good affinity for both the aqueous phase and the lipid bilayer, which is beneficial for permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, and rigidity, as well as its moderate polarity and neutral charge.

Final answer: High permeability

------
# 193

**SMILES:** CC1=CC=CC=C1C(=O)N2CCC(CC2)C(=O)N3CCC(CC3)N4CC5=CC=CC=C5C4=O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the 2-methylphenyl group and the isoindole moiety, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, as indicated by its molecular weight of 434. The size can affect permeability, but the presence of aromatic rings and the overall structure may still allow for sufficient permeation.

3. **Polarity**: The molecule has a low polar surface area, as suggested by the absence of multiple polar functional groups. This low polarity can contribute to higher permeability, as it allows the molecule to interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings and the isoindole structure suggests a degree of rigidity, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeation.

7. **Hydration Energy**: The molecule's structure, with limited polar groups, suggests a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to remove water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability.

Overall, the given molecule's structural features, including its lipophilicity, aromaticity, and rigidity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 194

**SMILES:** COC1=CC(=CC(=C1OC)OC)C(=O)NC2CCCC3=C2NC4=CC=CC=C34

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a trimethoxybenzamide moiety suggests that the molecule has a significant degree of lipophilicity. Methoxy groups are electron-donating, increasing the lipophilic character of the aromatic ring. This can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule contains a tetrahydrocarbazole moiety, which is a partially saturated polycyclic structure. This contributes to a relatively rigid and compact molecular framework. While the size of the molecule is moderate, the rigidity may help it to fit into the membrane more efficiently, potentially improving permeability.

3. **Polarity**: The trimethoxybenzamide portion of the molecule contributes to a relatively low polar surface area. The methoxy groups can engage in van der Waals interactions, but they do not significantly increase the overall polarity of the molecule. This low polarity can enhance membrane permeability by reducing the energy required for the molecule to traverse the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is favorable for permeability. Charged molecules often have reduced permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The tetrahydrocarbazole structure imparts a degree of rigidity to the molecule. This rigidity can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic benzamide component can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability. Aromatic rings are often involved in stacking interactions with the lipid tails, which can aid in membrane passage.

7. **Hydration Energy**: The presence of methoxy groups and the overall structure of the molecule suggest a lower hydration energy. This means the molecule is less likely to form strong interactions with water, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable membrane affinity. This balance allows the molecule to interact with both the aqueous environment and the lipid bilayer, enhancing its permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, aromaticity, and balanced membrane affinity.

Final answer: High permeability

------
# 195

**SMILES:** COC1=CC=CC=C1NC2=NC(=NC=C2)N3CCN(CC3)C(=O)C4=CC=C(C=C4)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the fluorophenyl and methoxyanilino groups, contributes to the lipophilic nature of the molecule. The fluorine atom on the phenyl ring can enhance lipophilicity due to its electronegativity, which can also influence the molecule's ability to interact with the lipid bilayer.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of multiple aromatic rings can help to compact the structure, potentially mitigating this effect.

3. **Polarity**: The methoxy group and the pyrimidinylpiperazine moiety introduce some degree of polarity. The methoxy group can form hydrogen bonds, which may enhance solubility in the aqueous phase, but the overall effect on permeability will depend on the balance with lipophilic components.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The aromatic rings and the pyrimidine core contribute to the rigidity of the molecule, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic systems present in the molecule can interact with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the methoxy and pyrimidinylpiperazine, may lead to moderate hydration energy, which can affect the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a moderate molecular size, and structural rigidity, which collectively suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 196

**SMILES:** COC1=CC=C(C=C1)C2=NC3=C(N2)C=CC=N3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an imidazopyridine derivative with a methoxyphenyl group attached. Let's analyze its properties to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the methoxyphenyl group contributes to the lipophilic character of the molecule. Methoxy groups are electron-donating, which can enhance the lipophilicity of the aromatic ring. This suggests that the given molecule may have a moderate to high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The imidazopyridine core is relatively small, and the addition of the methoxyphenyl group does not significantly increase the molecular size. This suggests that the molecule is likely to have a reasonable balance between size and permeability, favoring higher permeability.

3. **Polarity**: The methoxy group introduces some polarity, but the overall structure is dominated by the aromatic rings, which are hydrophobic. The low polar surface area and the presence of hydrogen bond acceptors (such as the nitrogen atoms in the imidazopyridine) suggest that the molecule may have moderate polarity, which could contribute to its permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the fused heterocyclic system contribute to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The aromatic and heterocyclic nature of the molecule suggests that it may have a lower hydration energy, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests that it may have a favorable membrane affinity, aiding in its permeability.

Overall, considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its moderate lipophilicity, balanced polarity, neutral charge, and structural rigidity.

Final answer: High permeability

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# 197

**SMILES:** CC1=CC(=NC=C1)NC(=S)N2CCCC(C2)NC3=CC=CC(=C3)C(F)(F)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and pyridinyl groups, contributes to the lipophilic nature of the molecule. The trifluoromethyl group on the pyridine ring further enhances lipophilicity due to its electron-withdrawing properties, which can increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of a piperidine ring, which is a saturated six-membered ring, can provide some flexibility and reduce steric effects, potentially allowing for better permeation.

3. **Polarity**: The molecule contains several polar groups, including the pyridine nitrogen atoms and the carbothioamide group. These polar groups can form hydrogen bonds and electrostatic interactions with the membrane, which may enhance permeability. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the piperidine ring contribute to a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous environment.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and polar interactions with the membrane.

Final answer: Low-to-moderate permeability

------
# 198

**SMILES:** COC1=CC=CC(=C1OC)CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC=CS3

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of methoxy groups on the phenyl ring increases the lipophilicity of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively complex, with multiple aromatic rings and a sulfonamide group. While the methoxy groups may increase lipophilicity, the larger size and weight of the molecule could limit its permeability due to steric hindrance and potential difficulty in passing through the membrane.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall balance of lipophilic and polar groups suggests moderate permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the hydrophobic lipid bilayer without encountering significant electrostatic barriers.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can also influence the molecule's lipophilicity and its ability to interact with the membrane, potentially enhancing its permeability.

7. **Hydration Energy**: The methoxy groups and the sulfonamide moiety may lower the hydration energy of the molecule, facilitating its passage through the membrane by reducing the energy required to overcome the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and structural complexity.

Final answer: Low-to-moderate permeability

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# 199

**SMILES:** C1=CC(=CC=C1NCC2=C(C=CC(=C2)Cl)O)S(=O)(=O)NC3=NC=CS3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chlorophenyl and thiazolyl groups, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings and functional groups, which may increase its molecular weight. However, the presence of aromatic rings and a sulfonamide group can also contribute to a compact structure, potentially mitigating the negative effects of size on permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic rings. The presence of a hydroxyl group also adds to the polarity, but the overall polar surface area is likely balanced by the lipophilic components.

4. **Charge**: The molecule is neutral, which is typical for many drug candidates, allowing it to traverse lipid membranes more effectively than charged molecules.

5. **Rigidity**: The aromatic rings and the thiazole moiety contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the hydroxyl and sulfonamide, may lead to moderate hydration energy, which can influence membrane permeation.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 200

**SMILES:** CN1CCN(CC1)C2=C(C=C(C=C2)NC3=NC(=NC4=CC=CC=C43)C5=CC=NC=C5)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the quinazoline and piperazine rings, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of multiple aromatic rings can help to compact the structure, potentially mitigating this effect.

3. **Polarity**: The molecule contains a methoxy group and a piperazine ring, which introduce some degree of polarity. The methoxy group can increase solubility in the aqueous phase, while the piperazine ring can participate in hydrogen bonding. These features may balance the lipophilicity and contribute to moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can interact with both the aqueous and lipid phases of the membrane.

5. **Rigidity**: The aromatic rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, enhancing membrane affinity and permeability.

7. **Hydration Energy**: The presence of polar groups, such as the methoxy and piperazine, may lower the hydration energy of the molecule, aiding in its permeation through the membrane.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability in PAMPA.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, along with structural features that promote membrane affinity and rigidity. These factors collectively suggest that the molecule would have moderate to high permeability in the PAMPA assay.

Final answer: High permeability

------
# 201

**SMILES:** CC1=CC=CC=C1C(=O)N2CCC3=C2C=CC(=C3)N4C=C(C=N4)NC(=O)CC5=CC=CC=C5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups and the indazole moiety, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with multiple aromatic and heterocyclic rings. While size can be a limiting factor for permeability, the presence of aromatic systems can also facilitate interactions with the lipid bilayer, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area due to the dominance of aromatic rings over polar functional groups. This low polarity is associated with higher permeability, as it allows the molecule to interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The indazole and phenyl rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings in the molecule can engage in π-π interactions with the lipid bilayer, which can enhance permeability by stabilizing the molecule within the membrane.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, facilitating its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule exhibits several structural characteristics that suggest it would have high permeability in the PAMPA assay, owing to its lipophilicity, aromaticity, rigidity, and favorable membrane interactions.

Final answer: High permeability

------
# 202

**SMILES:** CC1=C(C=CC=N1)C(=O)NC2=CC(=C(C=C2)OC)[S+](=O)(NC3=CC=C(C=C3)Br)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with multiple functional groups that can influence its permeability. Let's analyze the structural features to predict its permeability:

1. **Lipophilicity**: The presence of aromatic rings, such as the bromophenyl and pyridine groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer, as lipophilic compounds tend to dissolve better in lipid environments.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular structure due to the presence of multiple aromatic rings and functional groups. While size can be a limiting factor for permeability, the aromatic nature and potential for pi-pi interactions might help in crossing the membrane.

3. **Polarity**: The molecule contains polar functional groups such as the sulfonamide and amide linkages. These groups can form hydrogen bonds, which may aid in solubility in the aqueous phase and interaction with the membrane. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The balance of hydrophilic and hydrophobic groups suggests that the molecule may have moderate hydration energy, which can influence its permeability by affecting its interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The given molecule appears to have a balanced affinity for both the aqueous and lipid phases, which is indicative of good membrane permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and structural features that favor membrane interaction.

Final answer: High permeability

------
# 203

**SMILES:** CCC(CC)C1=NC(=NC(=C1)[C@H]2CN3CC[C@H]2C[C@@H]3CNC(=O)C)C4=CC=NC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as pyridine and pyrimidine, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule has a relatively large molecular weight and a bicyclic structure, which may limit its permeability due to steric hindrance. However, the specific bicyclic structure, azabicyclo[2.2.2]octane, is a rigid framework that can facilitate membrane permeation by reducing flexibility and conformational changes.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to its polar character. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can enhance permeability by allowing interaction with both the aqueous and lipid phases.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The azabicyclo[2.2.2]octane structure imparts rigidity to the molecule, which can improve its ability to permeate the membrane by maintaining a consistent conformation.

6. **Aromaticity**: The pyridine and pyrimidine rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of nitrogen atoms and aromatic rings suggests that the molecule may have moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests it has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for membrane permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a rigid structure, and a balanced affinity for the membrane, which collectively suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 204

**SMILES:** C1CCC(C(C1)C2C3=C(CCCC3=O)NC(=N2)NC4NC5CCCCC5S4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a cyclohexyl group and a quinazoline moiety suggests a significant degree of lipophilicity. These hydrophobic groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, as indicated by its molecular formula. While size can be a limiting factor for permeability, the presence of multiple rings and a rigid structure may help the molecule maintain a compact conformation, potentially mitigating size-related permeability issues.

3. **Polarity**: The molecule contains a tetrahydro-1,3-thiazolo[3,2-a]quinazoline ring system, which includes nitrogen and sulfur atoms. These heteroatoms can introduce some polarity, but the overall structure is likely dominated by its hydrophobic components, suggesting moderate to high lipophilicity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to traverse lipid membranes.

5. **Rigidity**: The presence of multiple fused rings, including aromatic and non-aromatic systems, contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The quinazoline moiety introduces aromatic character, which can further influence lipophilicity and membrane interactions, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, as it lacks highly polar or charged groups. This can facilitate its passage through the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, rigidity, and balanced polarity.

Final answer: High permeability

------
# 205

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)C2=CN=C(NC2=O)SC(C)C(=O)NC3=CC=CC=C3

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of a sulfonyl group attached to a phenyl ring (4-methylphenyl) suggests that the molecule has a significant degree of lipophilicity. This is because sulfonyl groups are relatively non-polar and can enhance the lipophilic character of the molecule.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings, including a pyrimidinyl and phenyl groups. While these rings contribute to the molecular weight, the overall size and weight are balanced by the presence of a smaller acetamide moiety. This balance suggests that the molecule is not excessively large, which is beneficial for permeability.

3. **Polarity**: The molecule contains a pyrimidinyl group, which can contribute to polarity. However, the overall polar surface area is moderated by the presence of non-polar aromatic rings and the sulfonyl group, which can reduce the overall polarity. The acetamide group also contributes to polarity, but its impact is somewhat mitigated by the surrounding hydrophobic groups.

4. **Charge**: The given molecule is neutral, as it does not contain any charged functional groups. This neutrality is favorable for permeability, as charged molecules often have reduced ability to permeate lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a pyrimidinyl ring suggests a degree of rigidity. This rigidity can enhance the ability of the molecule to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the molecule contribute to its lipophilicity and can facilitate interactions with the lipid bilayer through π-π interactions. This can enhance the permeability of the molecule.

7. **Hydration Energy**: The presence of sulfonyl and amide groups suggests that the molecule has a moderate hydration energy. This means that while it can interact with water, it is not overly hydrophilic, which is beneficial for membrane permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is ideal for permeability in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and structural rigidity.

Final answer: High permeability

------
# 206

**SMILES:** CC1=CC=CC=C1C(=O)NC2=NC3=C(S2)CC(CC3)C(C)(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a benzothiazole derivative with a tert-butyl group and a methylbenzamide moiety. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of the tert-butyl group and the benzothiazole core contributes to the lipophilic nature of the molecule. These groups increase the hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The benzothiazole core and the attached groups suggest a moderate molecular size. While larger molecules can have issues with permeability, the specific structure of the given molecule might still allow for sufficient diffusion through the artificial membrane.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic and aliphatic hydrocarbon groups. This low polarity can facilitate passage through the lipid-rich environment of the artificial membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers.

5. **Rigidity**: The benzothiazole ring system provides a degree of rigidity, which can help the molecule maintain a stable conformation as it interacts with the membrane. This rigidity can aid in permeability by reducing the likelihood of the molecule adopting a conformation that would hinder passage.

6. **Aromaticity**: The aromatic benzothiazole and benzamide components can interact with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is not strongly bound to water, which can facilitate its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests it has a favorable affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Overall, the given molecule's structural features, such as its lipophilicity, moderate size, and balanced polarity, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay.

Final answer: High permeability

------
# 207

**SMILES:** C1=CN(C(=C1)C=C2C(=O)NC(=S)NC2=O)C3=CC=C(C=C3)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the hydroxyphenyl group and the pyrrole moiety, contributes to the lipophilic character of the molecule. This can enhance its ability to interact with the lipid components of the artificial membrane, suggesting a potential for high permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the specific arrangement of functional groups and rings might allow for sufficient flexibility and conformational adaptability to traverse the membrane.

3. **Polarity**: The hydroxyphenyl group introduces a polar hydroxyl group, which can form hydrogen bonds. This may increase the molecule's solubility in the aqueous phase, potentially aiding in its permeability. However, the overall low polar surface area and the presence of non-polar aromatic rings suggest that the molecule's permeability is not significantly hindered by polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged species typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The pyrrole and aromatic rings contribute to a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural features that facilitate membrane interaction.

Final answer: High permeability

------
# 208

**SMILES:** C1COCCN1C2=NC=NC3=C2C=CC(=C3)NC(=O)C4=CC(=CC=C4)Br

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a quinazoline derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the quinazoline core and the bromobenzamide moiety, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The quinazoline core and the additional substituents, such as the morpholine ring, contribute to a relatively large molecular size. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may balance this out, potentially allowing for moderate permeability.

3. **Polarity**: The morpholine ring introduces some polarity due to its ether and amine functionalities. However, the overall structure is dominated by aromatic and heterocyclic components, which are generally more lipophilic. This suggests that the molecule may have a moderate polar surface area, which can influence its permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The quinazoline and aromatic benzamide structures contribute to a rigid molecular framework. This rigidity can enhance the ability of the molecule to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic nature of the quinazoline and benzamide rings can facilitate interactions with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups, such as the morpholine, may reduce the hydration energy of the molecule, aiding in its permeation through the membrane.

8. **Membrane Affinity**: The balance of lipophilic and polar characteristics suggests that the given molecule has a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability in PAMPA.

Overall, considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay.

Final answer: Moderate permeability.

------
# 209

**SMILES:** C1=CC=C(C(=C1)C2=NC=C(C(=N2)NCC3=CC=C(C=C3)C4=CC=NN4)F)C(F)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrazole and pyrimidine rings, contributes to the lipophilic nature of the molecule. Additionally, the fluoro substituent on the pyrimidine ring can enhance lipophilicity due to its electron-withdrawing properties, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to its polar character. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity. The presence of a trifluoromethyl group can also increase the molecule's lipophilicity, potentially offsetting the polar effects of the nitrogen atoms.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the pyrazole core provide a rigid structure, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability by stabilizing the molecule within the membrane.

7. **Hydration Energy**: The presence of fluorine atoms and aromatic structures can lower the hydration energy of the molecule, making it easier for the molecule to traverse the aqueous-lipid interface.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, as it possesses both lipophilic and polar characteristics, a balanced molecular size, and a neutral charge. However, its large and complex structure may limit its permeability compared to smaller or less complex molecules.

Final answer: Low-to-moderate permeability

------
# 210

**SMILES:** CC1=C(C=CN=C1)C2=NC3=CC=CC=C3C(=N2)NC4=CC(=C(C=C4)F)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a quinazoline derivative with several structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the quinazoline core and the pyridine rings, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and nitrogen atoms. While the size of the molecule is moderate, the presence of multiple rings and heteroatoms may limit its permeability compared to smaller, simpler molecules.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic rings, which are non-polar. However, the presence of nitrogen atoms can introduce some polarity, which may affect its interaction with the membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its lipophilicity and influence its interaction with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of nitrogen atoms and the overall structure of the molecule may result in moderate hydration energy, which can impact its permeability by affecting the energy required to remove water molecules from the surface of the molecule.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests it has a moderate affinity for the artificial membrane, which can result in moderate permeability.

Overall, the given molecule is likely to exhibit moderate permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and neutral charge.

Final answer: Low-to-moderate permeability

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# 211

**SMILES:** CN(C)C1=CC=CC=C1C2=CSC(=N2)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring, which is a heterocyclic compound containing both sulfur and nitrogen, contributes to the molecule's aromaticity and potential for electronic interactions. This can enhance the molecule's lipophilicity, which is generally associated with higher permeability.

The dimethylamino group attached to the phenyl ring introduces a degree of basicity and polarity to the molecule. This group can participate in hydrogen bonding and ionic interactions, which may affect the molecule's solubility and permeability. However, the dimethylamino group also increases the overall polarity of the molecule, which can limit its permeability due to reduced solubility in the lipid bilayer.

The piperidine ring is a saturated six-membered ring that contributes to the molecule's overall rigidity and structural stability. This rigidity can enhance the molecule's ability to permeate the membrane by reducing its conformational flexibility, which can otherwise hinder passage through the lipid bilayer.

Overall, the given molecule's structure suggests a balance of lipophilic and polar characteristics, with aromatic and rigid components that may enhance its permeability. However, the presence of polar groups and the overall molecular size may limit its permeability to some extent. Therefore, the given molecule is likely to exhibit moderate permeability in the PAMPA assay.

Final answer: Low-to-moderate permeability

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# 212

**SMILES:** CC1=CC=C(C=C1)NC(=O)C2=C3NC(=C(C(N3N=C2)C4=CC=CC=C4C)C(=O)NC5=CC=C(C=C5)Cl)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA). Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the 4-chlorophenyl and 2-methylphenyl groups, contributes to the lipophilic nature of the molecule. These aromatic rings increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular structure due to its multiple aromatic rings and heterocyclic components. While size can be a limiting factor for permeability, the specific arrangement and rigidity of the pyrazolo[1,5-a]pyrimidine core may allow for sufficient flexibility to traverse the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the dominance of aromatic hydrocarbons over polar functional groups. This low polarity is beneficial for permeability as it allows the molecule to interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is advantageous for permeability as charged molecules often face significant barriers in crossing lipid membranes due to their inability to interact with the hydrophobic lipid bilayer.

5. **Rigidity**: The pyrazolo[1,5-a]pyrimidine core provides a degree of rigidity to the molecule, which can enhance its ability to permeate the membrane by reducing the energy required for conformational changes during transport.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also may engage in π-π interactions with the lipid bilayer, potentially aiding in membrane permeation.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less tightly bound to water molecules, facilitating its passage through the aqueous environment surrounding the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests a favorable membrane affinity, which is essential for effective permeation.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and favorable balance of hydrophobic and hydrophilic interactions.

Final answer: High permeability

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# 213

**SMILES:** CC1=C(C=CC=C1Cl)N2C(=C(C=N2)C(=O)NC3=C(C=C(C=C3)Br)F)C4CCNCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyrazole rings, contributes to the lipophilic nature of the molecule. Additionally, the bromo and chloro substituents on the phenyl ring increase the lipophilicity due to their electron-withdrawing properties, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular structure due to the presence of multiple aromatic rings and a carboxamide group. This size can potentially limit its permeability, as larger molecules may have difficulty traversing the membrane.

3. **Polarity**: The carboxamide group introduces some polarity to the molecule, which can affect its solubility and permeability. However, the overall lipophilicity due to the aromatic rings and halogen substituents likely dominates, suggesting moderate to high permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can facilitate interactions with the lipid bilayer through π-π interactions, potentially enhancing its permeability.

7. **Hydration Energy**: The presence of halogen atoms and aromatic rings suggests that the hydration energy of the molecule is relatively low, which can improve its permeability by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable membrane affinity, which is beneficial for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and balanced polarity.

Final answer: High permeability

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# 214

**SMILES:** CCOC(=O)N1CCC2=C(C1)SC(=C2C(=O)NC3=C(C=CC(=C3)Cl)OC)NCC4=C(C=CS4)C

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the methoxy-chlorophenyl group and the thiazole ring, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help to maintain some degree of rigidity, which can improve permeability.

3. **Polarity**: The molecule contains several polar groups, including the methoxy group, the carbonyl groups, and the thiazole ring. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting that the polar surface area is not excessively high, which could favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The thiazole ring and the aromatic systems contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings, including the chlorophenyl and thiazole, can interact with the lipid bilayer, potentially enhancing permeability through hydrophobic interactions.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous phase.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, balanced polarity, rigidity, and favorable interactions with the lipid bilayer.

Final answer: High permeability

------
# 215

**SMILES:** C1CCN(CC1)C(=O)C2=CC3=C(C=C2)N(C=N3)C4=CC=C(C=C4)Cl

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chlorophenyl group contributes to the lipophilic nature of the molecule. This group can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The benzimidazole moiety introduces some degree of polarity to the molecule. However, the overall polarity is balanced by the lipophilic chlorophenyl group, suggesting moderate polarity. This balance can favor moderate permeability, as the molecule can interact with both hydrophilic and hydrophobic environments.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The benzimidazole and chlorophenyl groups contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation while interacting with the membrane.

6. **Aromaticity**: The aromatic rings present in the structure can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The presence of polar groups and aromatic rings suggests that the hydration energy of the molecule is moderate. This can influence its ability to permeate the membrane, as lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and rigidity, along with the presence of aromatic rings, suggests that it can interact effectively with the artificial membrane, but its size and complexity may limit its permeability to some extent.

Final answer: Low-to-moderate permeability

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# 216

**SMILES:** CNC1=C(N=C(O1)C2=C(C(=CC=C2)Cl)Cl)C#N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of dichlorophenyl groups contributes to the molecule's lipophilicity. Chlorine atoms increase the hydrophobic character of the molecule, which can enhance its ability to permeate lipid membranes. This is because lipophilic molecules can more easily dissolve in the lipid bilayer of the artificial membrane.

Secondly, the oxazole ring is a heterocyclic aromatic compound that can also contribute to the molecule's lipophilicity. Aromatic rings often enhance membrane permeability due to their ability to interact with the lipid bilayer through π-π interactions.

The methylamino group introduces a degree of polarity to the molecule, which can affect its solubility and permeability. However, in this case, the balance of hydrophobic and hydrophilic properties suggests that the molecule's overall lipophilicity is higher than its polarity, which may favor permeability.

The nitrile group (carbonitrile) is a polar functional group, but its presence is relatively small compared to the overall structure, and it may not significantly hinder permeability due to its linear nature.

The molecule's molecular size and weight are relatively low, which generally correlates with higher permeability. Additionally, the molecule is neutral, which is favorable for permeability as charged molecules often have reduced diffusion through lipid membranes.

Overall, the given molecule's structural features, including its lipophilicity, aromaticity, and moderate polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 217

**SMILES:** CC1=C(C(=NO1)C2=CC=C(C=C2)F)COC3=NC=C(C=C3)C(=O)N4CCS(=O)(=O)CC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and isoxazole groups, contributes to the lipophilic nature of the molecule. The fluorine atom on the phenyl ring can enhance lipophilicity due to its electronegativity, which can increase the molecule's ability to interact with the lipid components of the membrane.

2. **Molecular Size and Weight**: The overall size of the molecule is relatively large due to the presence of multiple rings and functional groups. This can potentially limit its permeability, as larger molecules may have difficulty traversing the membrane.

3. **Polarity**: The molecule contains polar groups such as the pyridine ring and the sulfonyl group. However, the overall polar surface area is balanced by the lipophilic aromatic rings, which may allow the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous phase.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for membrane permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, neutral charge, and structural rigidity, which facilitate its interaction with the artificial membrane.

Final answer: High permeability

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# 218

**SMILES:** CN1C=NC=C1[C@@](C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC(=CC=C5)Cl)C)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl and quinoline rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and a complex structure, which may limit its permeability due to size constraints. Larger molecules often have reduced permeability as they may face steric hindrance when passing through the artificial membrane.

3. **Polarity**: The molecule contains several polar groups, including an amino group and a methylimino group. However, the overall polar surface area is balanced by the extensive aromatic system, which may reduce the molecule's polarity. This balance suggests moderate polarity, which can influence permeability by allowing some interaction with the membrane while maintaining sufficient lipophilicity.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The quinoline core provides a rigid structure, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its ability to permeate the membrane by affecting its solubility and interaction with water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the molecule suggests that it may have a favorable affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable structural rigidity.

Final answer: High permeability

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# 219

**SMILES:** C1=CC(=CC(=C1)F)NC(=O)C2=CC(=NN2)C3=CC=CN3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyrrolyl groups, contributes to the lipophilicity of the molecule. Aromatic rings are known to enhance lipophilicity, which generally increases permeability up to a certain threshold. However, the balance with other polar groups will determine the overall permeability.

2. **Molecular Size and Weight**: The given molecule has a moderate molecular size and weight due to the presence of multiple aromatic rings and heterocycles. While size can limit permeability, the specific arrangement and connectivity of these rings may still allow for sufficient permeation.

3. **Polarity**: The molecule contains a fluorophenyl group, which introduces a fluorine atom. Fluorine can increase lipophilicity while also affecting electronic properties, potentially enhancing membrane permeability. Additionally, the carboxamide group contributes to polarity, but its presence is balanced by the lipophilic aromatic systems.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to the rigidity of the molecule. Rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic nature of the molecule can influence its interaction with the lipid bilayer, potentially enhancing permeability through favorable π-π interactions with the membrane.

7. **Hydration Energy**: The presence of polar groups like the carboxamide may reduce hydration energy, which can improve membrane permeation by reducing the energy required to pass through the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable structural features for membrane interaction.

Final answer: High permeability

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# 220

**SMILES:** COC1=NC=C(C=C1)C2=CC(=CN3C2=CN=C3)C4=C5C=NNC5=CC=C4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including pyridine and indole, suggests a high degree of lipophilicity. Aromatic rings are known to enhance lipophilicity, which generally increases permeability up to a certain threshold.

2. **Molecular Size and Weight**: The given molecule is relatively large, as indicated by its molecular weight of 327.3 g/mol. Large molecules often have reduced permeability due to size limitations in crossing biological membranes. However, the specific arrangement of functional groups and rings can influence this.

3. **Polarity**: The pyridine and indole rings contribute to the overall polarity of the molecule. The pyridine ring, in particular, can introduce some degree of polarity. However, the overall structure is dominated by aromatic systems, which are generally lipophilic.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to permeate lipid bilayers.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule. Rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The presence of multiple aromatic systems, including pyridine and indole, suggests significant aromaticity. Aromaticity can influence both lipophilicity and the ability to interact with the lipid bilayer.

7. **Hydration Energy**: The aromatic nature of the molecule suggests a lower hydration energy, which can improve membrane permeation as it reduces the energy required to cross the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, aromaticity, and balanced polarity.

Final answer: High permeability

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# 221

**SMILES:** CC(C)OC1=CC=C(C=C1)CNC(=O)C2CCN(CC2)C(=O)N3CCOC4=C3C=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chlorophenyl group and the benzoxazine moiety, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic rings and the overall structure may allow for sufficient flexibility to traverse the membrane.

3. **Polarity**: The molecule contains several polar groups, including the carboxamide and the piperidine ring. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings and the benzoxazine structure contribute to a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can influence its interaction with the aqueous environment and the lipid membrane.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic components suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and favorable interactions with the artificial membrane.

Final answer: High permeability

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# 222

**SMILES:** CC1=CC(=C(C=C1)C)NC2=C(C(=O)C3=CC=CC=C32)C4=CC=C(C=C4)C(F)(F)F

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the trifluoromethylphenyl and dimethylphenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the pores of the artificial membrane.

3. **Polarity**: The molecule contains a fluorine atom and several aromatic rings, which contribute to its overall low polar surface area. The trifluoromethyl group is particularly hydrophobic, reducing the polar character of the molecule. This low polarity can enhance permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules are less likely to diffuse through the lipid bilayer due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The presence of multiple aromatic rings imparts a degree of rigidity to the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability. However, this effect can be balanced by the size and hydrophobicity of the molecule.

7. **Hydration Energy**: The trifluoromethyl group and other hydrophobic components of the molecule likely lower its hydration energy, making it easier for the molecule to traverse the aqueous environment surrounding the membrane and interact with the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests it has a favorable membrane affinity, which can enhance its permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, neutral charge, and favorable interactions with the lipid bilayer.

Final answer: High permeability

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# 223

**SMILES:** C1CCN(C1)C(=O)C2=NC(=C3N2C=CC=C3)C4=CN=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and imidazo[1,2-a]pyridine moieties, suggests that the molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, as indicated by its molecular weight of 335.4 g/mol. While size can be a limiting factor for permeability, the presence of multiple aromatic rings and heterocycles may allow for some degree of flexibility and conformational adaptability, which can mitigate this effect.

3. **Polarity**: The molecule has a low polar surface area, which is a result of the aromatic and heterocyclic structures. This low polarity suggests that the molecule can interact favorably with the hydrophobic environment of the lipid bilayer, enhancing its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings contributes to a relatively rigid structure. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing the molecule's affinity for the membrane and thus its permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less likely to form strong interactions with water, which can facilitate its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, aromaticity, and favorable balance of hydrophobic and hydrophilic interactions.

Final answer: High permeability

------
# 224

**SMILES:** C1=CC=C2C(=C1)N=C3C=CC=C(C3=N2)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule, phenazine-1-ol, is characterized by its phenazine core, which is a tricyclic aromatic system. This structure contributes to its lipophilicity, as aromatic systems are generally hydrophobic. The presence of the hydroxyl group (the -ol suffix) adds a degree of polarity, but the overall structure remains predominantly lipophilic due to the extensive aromatic system.

The molecule's size and weight are relatively moderate, which suggests that while it may not permeate as easily as very small molecules, it should still have sufficient permeability. The hydroxyl group can form hydrogen bonds, which may facilitate interactions with the artificial membrane, potentially enhancing permeability.

The molecule is neutral, which is favorable for permeability as charged species typically have lower permeability due to their inability to diffuse through the lipid bilayer. The aromatic rings contribute to the rigidity of the molecule, which can improve its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

Overall, the given molecule's lipophilicity, moderate size, neutral charge, and rigid aromatic structure suggest that it would have high permeability in the Parallel Artificial Membrane Permeability Assay.

Final answer: High permeability

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# 225

**SMILES:** COC1=CC=CC(=C1CNC2=CC=C(C=C2)S(=O)(=O)NC3=NC=CS3)O

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule contains a relatively complex structure with multiple rings and functional groups, which may increase its molecular weight. However, the presence of aromatic rings and a sulfonamide group can also contribute to a compact structure, potentially mitigating the negative effects of size on permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic rings. The methoxy group also adds to the polarity, but the overall polar surface area is likely balanced by the non-polar regions, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is typical for many drug candidates, allowing it to traverse lipid membranes more effectively than charged molecules.

5. **Rigidity**: The aromatic rings and the thiazole moiety contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The balance of hydrophilic and hydrophobic groups suggests that the molecule may have a moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the membrane.

8. **Membrane Affinity**: The combination of lipophilic and polar features suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is favorable for membrane permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and structural rigidity.

Final answer: High permeability

------
# 226

**SMILES:** C1CN(CCN(C1)C2=NC=C(C=C2)C(F)(F)F)CC3=CC(=O)N4C=CC=CC4=N3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a trifluoromethyl group contributes to the lipophilic nature of the molecule. This group is known for increasing lipophilicity due to its electron-withdrawing properties, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The overall size of the molecule, including the piperidine and pyrido[1,2-a]pyrimidine rings, suggests a moderate molecular weight. While larger molecules can have reduced permeability due to size constraints, the specific arrangement of these rings may allow for sufficient flexibility and conformational adaptability to traverse the membrane.

3. **Polarity**: The molecule contains a pyrido[1,2-a]pyrimidine-2-one moiety, which contributes to its polar characteristics. However, the overall polar surface area is balanced by the lipophilic trifluoromethyl group, suggesting a moderate polarity that may not hinder permeability significantly.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The presence of aromatic rings, such as the pyrido[1,2-a]pyrimidine and piperidine rings, introduces rigidity to the structure. This rigidity can enhance the molecule's ability to fit into the membrane's lipid bilayer, potentially improving permeability.

6. **Hydration Energy**: The trifluoromethyl group can lower the hydration energy of the molecule, making it easier for the molecule to transition from an aqueous environment to a lipid environment, which is crucial for membrane permeability.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases of the membrane.

Overall, the given molecule's structural features, including its lipophilicity, moderate size, balanced polarity, and favorable membrane interactions, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 227

**SMILES:** CC(C)(C)C1=CC=C(C=C1)C(=O)N2CC(=O)NC3=C(C2C4=CC=C(C=C4)F)C=C(C=C3)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a benzodiazepine derivative, which is a class of compounds known for their central nervous system activity. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups and the benzodiazepine core, contributes to the lipophilic nature of the molecule. The fluorine atoms on the benzodiazepine ring and the phenyl group can enhance lipophilicity due to their electronegativity, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The benzodiazepine core and the attached phenyl groups suggest a relatively large molecular size. However, the presence of fluorine atoms and the overall planar structure of the benzodiazepine may reduce steric hindrance, allowing for some flexibility in permeation.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic rings and the presence of fluorine, which can reduce hydrogen bonding potential. This low polarity is beneficial for permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is typical for benzodiazepines, allowing it to traverse the lipid bilayer without significant resistance due to charge repulsion.

5. **Rigidity**: The benzodiazepine core is relatively rigid, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and can engage in π-π interactions with the lipid bilayer, enhancing permeability.

7. **Hydration Energy**: The presence of fluorine and the overall structure suggests a lower hydration energy, which can improve membrane permeation by reducing the energy required to remove water molecules from the molecule.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests a favorable membrane affinity, which is essential for its permeability in the PAMPA assay.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, structural rigidity, and membrane affinity.

Final answer: High permeability

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# 228

**SMILES:** CC1=CN=C(N=C1C2=CC(=CC=C2)N(C)C)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a pyrimidine derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a dimethylamino group attached to a phenyl ring increases the lipophilicity of the molecule. This group can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively complex, with a piperidine ring and a pyrimidine core. While these rings contribute to the molecular weight, the presence of aromatic and heterocyclic rings can also influence the molecule's ability to fit into the membrane pores, potentially affecting permeability.

3. **Polarity**: The molecule contains a carboxamide group, which can introduce some degree of polarity. However, the overall effect of this group on permeability is balanced by the lipophilic phenyl and pyrimidine rings, which dominate the molecule's surface characteristics.

4. **Charge**: The dimethylamino group can impart a slight positive charge to the molecule, which may enhance its interaction with the negatively charged lipid bilayer. However, the overall charge distribution is neutral, which is favorable for permeability.

5. **Rigidity**: The aromatic rings and heterocyclic structures contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The phenyl and pyrimidine rings contribute to the aromatic character of the molecule. Aromaticity can enhance lipophilicity and facilitate interactions with the hydrophobic regions of the membrane, potentially increasing permeability.

7. **Hydration Energy**: The presence of both hydrophobic and hydrophilic regions in the molecule suggests that it may have a moderate hydration energy. This balance can aid in its permeation through the membrane by allowing it to interact with both aqueous and lipid environments.

8. **Membrane Affinity**: The given molecule's structure suggests a balanced affinity for both the aqueous phase and the lipid bilayer, which is indicative of good permeability in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and favorable structural characteristics for membrane interaction.

Final answer: High permeability

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# 229

**SMILES:** C1=CC=NC(=C1)N[S+](=O)(C2=CC=C(C=C2)NC(=O)CC3=CC(=C(C=C3)Cl)Cl)[O-]

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is characterized by several structural features that influence its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Firstly, the presence of dichlorophenyl groups contributes to the lipophilicity of the molecule. Chlorine atoms increase the hydrophobic character, which generally enhances membrane permeability up to a certain point. However, if the molecule becomes too lipophilic, it may not be soluble in the aqueous environment, potentially reducing permeability.

Secondly, the molecule contains a sulfonamide group, which is polar and can form hydrogen bonds. This group can interact with the polar head groups of the artificial membrane, potentially improving permeability by facilitating interactions with the membrane.

The pyridinyl moiety introduces aromaticity and basicity to the molecule. Aromatic rings can enhance lipophilicity, but the presence of nitrogen in the pyridine ring can also participate in hydrogen bonding and ionic interactions, which may balance the overall permeability.

The acetamide linkage contributes to the molecule's polarity and ability to form hydrogen bonds. This can enhance solubility in the aqueous phase, which is crucial for permeability.

Overall, the given molecule exhibits a balance of hydrophobic and hydrophilic properties, with aromatic and polar functional groups that suggest moderate permeability. The dichlorophenyl groups increase lipophilicity, while the sulfonamide and pyridinyl groups provide polar interactions. These features collectively suggest that the molecule would exhibit moderate permeability in the PAMPA assay.

Final answer: Low-to-moderate permeability

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# 230

**SMILES:** CC(=O)NC1=CC=C(C=C1)NC(=O)C(C2=CC=CC=C2)NS(=O)(=O)C3=CC=C(S3)Br

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of a bromophenyl group and a phenylthiophene moiety suggests that the given molecule has significant lipophilic characteristics. These aromatic groups contribute to the overall hydrophobic nature, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434.38 g/mol. While size is a limiting factor for permeability, the presence of aromatic rings and the sulfonamide group may help in maintaining a balance that allows for sufficient permeability.

3. **Polarity**: The acetamido group and the sulfonamide moiety introduce polar characteristics to the molecule. However, the overall polar surface area is balanced by the lipophilic aromatic rings, which may not significantly hinder permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have reduced diffusion through lipid membranes.

5. **Rigidity**: The aromatic rings and the sulfonamide linkage contribute to a rigid structure, which can facilitate membrane permeation by reducing the flexibility that might otherwise hinder passage through the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl and thiophene groups, can enhance lipophilicity and influence interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The given molecule's structure suggests a relatively low hydration energy due to its balance of hydrophilic and hydrophobic groups, which can favor membrane permeation.

8. **Membrane Affinity**: The combination of hydrophobic and hydrophilic elements in the given molecule suggests a balanced affinity for both the aqueous and lipid phases, which is typically favorable for permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable structural characteristics for membrane interaction.

Final answer: High permeability

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# 231

**SMILES:** CC1=CC(=C(N1C2=CC=CC(=C2)C#N)C)C3=NN=C4N3CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a nitrile group attached to a benzene ring and the overall aromatic structure contribute to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and a complex structure. While size can be a limiting factor for permeability, the presence of aromatic rings and heterocyclic structures may help to maintain some degree of permeability due to their planar nature.

3. **Polarity**: The molecule contains a nitrile group, which is polar, and a triazolopyridine moiety, which can also contribute to polarity. However, the overall polar surface area is relatively low due to the dominance of aromatic and hydrocarbon components, suggesting that the molecule may have a balanced polarity that supports permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the triazolopyridine moiety contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The aromatic and hydrocarbon components suggest that the molecule may have a lower hydration energy, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it may have a favorable membrane affinity, aiding in its permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable structural rigidity and aromaticity.

Final answer: High permeability

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# 232

**SMILES:** COC1=C(C=CC(=C1)/C=C(\C#N)/C2=NC3=CC=CC=C3N2)OCC4=CC=C(C=C4)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of methoxy groups and a fluorophenyl moiety contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall size of the molecule is moderate, with a significant aromatic system. While the size is not excessively large, the presence of multiple aromatic rings and a nitrile group may limit its permeability compared to smaller molecules.

3. **Polarity**: The methoxy and fluorophenyl groups contribute to the molecule's polarity, but the overall polarity is balanced by the presence of aromatic rings and a nitrile group. This balance can result in moderate permeability, as the molecule can interact with both hydrophilic and hydrophobic environments.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can diffuse more easily through the lipid bilayer without being repelled by charges.

5. **Rigidity**: The presence of aromatic rings and a conjugated system contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the molecule can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The presence of polar groups like methoxy and nitrile may lead to moderate hydration energy, which can affect the molecule's ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic groups suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, rigidity, and membrane affinity that facilitates its passage through the artificial membrane.

Final answer: Moderate permeability.

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# 233

**SMILES:** CCN(CC)CCN1C2=C(C=CC(=C2)OCCN(CC)CC)C(=O)C3=C1C=C(C=C3)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an acridine derivative, which is a class of compounds known for their planar aromatic structures. This particular molecule has several key structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the acridine core, which is a polycyclic aromatic structure, contributes to the lipophilicity of the molecule. This enhances its ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Aromaticity**: The acridine moiety is highly aromatic, which can facilitate interactions with the lipid bilayer through π-π stacking and van der Waals forces. This can enhance the molecule's ability to permeate the membrane.

3. **Substituents**: The molecule contains a diethylaminoethoxy group, which introduces some degree of polarity. However, the ethoxy linkage and the diethylamino group are relatively small and may not significantly hinder permeability due to their flexibility and ability to adapt to the membrane structure.

4. **Chlorine Substitution**: The chlorine atom on the acridine ring can increase the lipophilicity further and may also participate in halogen bonding, which can stabilize interactions with the membrane.

5. **Overall Structure**: The combination of the acridine core with the diethylaminoethoxy substituent suggests that the molecule has a balanced lipophilic and hydrophilic character, which is often favorable for membrane permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic aromatic core, balanced substituents, and the presence of a chlorine atom.

Final answer: High permeability

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# 234

**SMILES:** CN1C=C(C(=N1)C2C3=C(CCCC3=O)NC(=N2)NC4=NC5=CC=CC=C5O4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chloro group and multiple aromatic rings, such as the quinazoline and oxadiazole rings, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 344.35 g/mol. While size is a factor in permeability, the presence of multiple rings and heteroatoms may allow for some flexibility, which can mitigate the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of non-polar aromatic rings and the chloro substituent. This low polarity contributes to its ability to permeate the membrane, as it can interact favorably with the hydrophobic lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles contributes to a degree of rigidity, which can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation during passage.

6. **Aromaticity**: The quinazoline and oxadiazole rings contribute to the molecule's aromatic character, which can influence its lipophilicity and interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it can easily transition from an aqueous environment to a lipid environment, facilitating membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is conducive to high permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay, as it possesses a combination of lipophilicity, aromaticity, and a balanced polarity that favor membrane permeation.

Final answer: High permeability

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# 235

**SMILES:** CNC1=NC=CC(=N1)C2=CC=CC3=CC=CC=C32

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of quinoline, which is a heterocyclic aromatic compound. The structure of the molecule includes a quinoline moiety, which contributes to its aromaticity and potential for hydrophobic interactions. This aromatic system can enhance the molecule's lipophilicity, which is a key factor in determining its permeability.

Additionally, the molecule contains a pyrimidine ring, which is a nitrogen-containing heterocycle. The presence of nitrogen atoms in the pyrimidine ring can introduce some degree of polarity, but the overall structure is likely dominated by the lipophilic quinoline component.

The N-methyl group attached to the pyrimidine ring can further influence the molecule's lipophilicity and steric properties. This methyl group may enhance the molecule's ability to interact with the lipid bilayer, potentially increasing its permeability.

Overall, the combination of aromaticity, lipophilicity, and the balance of polar and non-polar regions in the given molecule suggests that it would exhibit high permeability in the PAMPA assay. The molecule's structure allows it to effectively interact with the hydrophobic environment of the artificial membrane, facilitating its passage through the membrane.

Final answer: High permeability

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# 236

**SMILES:** CC1=CC2=C(C=C1)OC3=C(C2=O)C(N(C3=O)CCCN4CCOCC4)C5=CC(=C(C=C5)OC)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of methoxy groups on the phenyl ring and the methyl group on the chromenone core contribute to the lipophilic character of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the balance of lipophilic and hydrophilic groups can still allow for sufficient permeation.

3. **Polarity**: The methoxy groups and the chromenone core contribute to the molecule's polarity, but the overall structure is balanced with lipophilic components, suggesting moderate polarity. This balance can favor permeability through the membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The chromenone core provides a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing flexibility and potential entanglement with the membrane.

6. **Aromaticity**: The aromatic phenyl and chromenone rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The presence of methoxy groups and the overall structure suggest a lower hydration energy, which can improve membrane permeation by reducing the energy required to cross the membrane.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and structural rigidity.

Final answer: High permeability

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# 237

**SMILES:** COC1=CC=C(C=C1)NC2=C(C(=O)C3=CC=CC=C32)C4=CC=C(C=C4)C(F)(F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of trifluoromethyl groups contributes to the molecule's lipophilicity. These groups are known to enhance the hydrophobic character of a molecule, which can increase its ability to permeate lipid membranes. This is because lipophilic molecules can more easily dissolve in the lipid bilayer of the artificial membrane.

Secondly, the indene core of the molecule provides a degree of rigidity and aromaticity. Aromatic rings, such as those in the indene structure, can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability. However, the rigidity of the indene structure may also limit the molecule's flexibility, which can either hinder or facilitate permeability depending on the balance with other factors.

The presence of the methoxyanilino group introduces a polar element to the molecule. While this could potentially decrease permeability due to increased polarity, the methoxy group is relatively small and may not significantly hinder permeability. The balance between the polar and non-polar regions of the molecule will dictate its overall permeability.

Additionally, the molecule is neutral, which is generally favorable for permeability as charged molecules often have reduced ability to permeate lipid membranes.

Overall, the given molecule's combination of lipophilic trifluoromethyl groups, aromatic indene core, and polar methoxyanilino group suggests that it would exhibit high permeability in the PAMPA assay. The balance of these features likely allows the molecule to effectively interact with the artificial membrane, facilitating its passage through it.

Final answer: High permeability

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# 238

**SMILES:** CCN(CC)CCCC(C)NC1=C2C=CC(=CC2=NC(=C1)/C=C/C3=CC=CC=C3Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinoline derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the quinoline moiety, which is a planar aromatic system, contributes to the lipophilicity of the molecule. This aromatic system can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.5 g/mol. While size is a factor in permeability, the presence of multiple functional groups and aromatic rings may allow for specific interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is indicated by the low number of hydrogen bond donors and acceptors. This low polarity suggests that the molecule is more lipophilic, favoring permeability through the hydrophobic membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of lipids.

5. **Rigidity**: The quinoline core provides a rigid structure, which can facilitate passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The quinoline and chlorophenyl groups contribute to the aromatic character, enhancing lipophilicity and potentially allowing for π-π interactions with the membrane.

7. **Hydration Energy**: The low hydration energy suggests that the molecule is less tightly bound to water molecules, which can enhance its ability to permeate the membrane by reducing the energy required for desorption from the aqueous phase.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests a moderate affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that favor high permeability in the PAMPA assay.

Final answer: High permeability

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# 239

**SMILES:** CC1=C(C=CC(=C1)Br)NC(=O)C(C2=CC=CC=C2)NS(=O)(=O)C3=CC=CS3

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of a bromophenyl group and a phenyl group suggests that the molecule has significant lipophilic characteristics. These aromatic rings contribute to the overall hydrophobic nature, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a sulfonamide group. While the aromatic rings increase lipophilicity, the overall size and weight may limit permeability due to steric hindrance and potential difficulty in crossing the membrane.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall effect of the lipophilic aromatic rings may dominate, leading to higher permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings contributes to the rigidity of the molecule. This rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The sulfonamide group may have a moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and balanced polarity.

Final answer: High permeability

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# 240

**SMILES:** COC1=CC2=C(C=C1)C(=C(N2CC3=CC=C(C=C3)C=C)C(=O)O)CNC4CCCCC4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a methoxy group and an aromatic phenyl ring contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a cyclohexyl group and an indole moiety, which contribute to its hydrophobic character. However, the presence of a carboxylic acid group introduces some polarity. The balance between these hydrophobic and polar regions will influence the overall permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The indole core provides a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent shape that can interact effectively with the membrane.

6. **Aromaticity**: The phenyl and indole rings contribute to the aromatic character of the molecule, which can enhance lipophilicity and facilitate interactions with the lipid bilayer.

7. **Hydration Energy**: The presence of polar groups like the carboxylic acid and the methoxy group may lead to moderate hydration energy, which can affect the molecule's solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilic and polar groups, along with the structural rigidity and aromaticity, suggests that it can interact effectively with the artificial membrane, but the larger size may limit its permeability compared to smaller molecules.

Final answer: Low-to-moderate permeability

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# 241

**SMILES:** CCN1C=C(C2=CC(=C(C=C2C1=O)OC)OC)C(=O)N3CCN(CC3)C4=CC(=CC=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of methoxy groups and an isoquinoline core contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall size of the molecule, including the piperazine and isoquinoline rings, suggests a moderate molecular weight. While larger molecules can have reduced permeability due to size constraints, the specific arrangement of these rings might allow for sufficient permeation.

3. **Polarity**: The molecule contains a chlorophenyl group, which adds to the lipophilicity, while the piperazine ring introduces some polarity. The balance between these features suggests that the molecule may have moderate polarity, which can influence its permeability by allowing some interaction with the aqueous phase while maintaining sufficient lipophilicity for membrane passage.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The isoquinoline and piperazine rings contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by reducing the flexibility that might otherwise hinder passage.

6. **Aromaticity**: The aromatic rings, including the isoquinoline and chlorophenyl groups, can interact with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of methoxy groups and the overall structure suggest that the molecule has a relatively low hydration energy, which can facilitate its passage through the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a balanced affinity for both the aqueous and lipid phases, which is often desirable for good permeability in PAMPA assays.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and structural rigidity.

Final answer: High permeability

------
# 242

**SMILES:** C1=CC=C(C=C1)C2=CSC(=N2)NC(=O)C3=C(C=NC=C3)NS(=O)(=O)C4=CC=CC=C4C#N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine groups, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. This could potentially limit its permeability due to steric hindrance, but the aromatic and heterocyclic components may help to balance this effect.

3. **Polarity**: The sulfonamide group introduces some polarity, but the overall structure is dominated by aromatic and heterocyclic components, which are less polar. The low polar surface area and the presence of hydrogen bond acceptors (such as the pyridine nitrogen) suggest that the molecule may have moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and conformational changes.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The sulfonamide and aromatic groups may lower the hydration energy, making it easier for the molecule to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 243

**SMILES:** CCN1CCC(CC1)N(CC2=CC3=C(C=C2)OCO3)C(=O)NC4=C(C=CC(=C4)Cl)C(=O)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzodioxole and benzene rings, contributes to the lipophilic nature of the molecule. Additionally, the ester group (methyl ester) and the chloro substituent on the benzene ring further enhance lipophilicity. These features suggest that the molecule is likely to have a high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic rings and the piperidine moiety may help to maintain a balance, allowing for sufficient permeability despite the size.

3. **Polarity**: The molecule contains several polar groups, including the ester and amide linkages, as well as the piperidine ring. However, the overall polar surface area is relatively low due to the dominance of aromatic and hydrophobic groups. This suggests that the molecule may have moderate polarity, which can influence its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the piperidine moiety contribute to a degree of rigidity in the molecule. This rigidity can enhance the ability of the molecule to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The molecule's structure, with its hydrophobic and aromatic components, suggests that it may have a lower hydration energy. This can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 244

**SMILES:** CCOC1=C(C=C(C=C1)CCNC(=O)C2=CC3=C(N2CC4=CC=CC(=N4)C)C=CC=N3)OCC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of ethoxy and methyl groups on the phenyl ring and the pyridine moiety suggests that the molecule has a moderate to high lipophilicity. This is because these groups are non-polar and contribute to the overall hydrophobic character of the molecule.

2. **Molecular Size and Weight**: The molecule contains multiple aromatic rings, including a pyridine and a phenyl ring, which contribute to its molecular size. While the aromatic rings increase the molecular weight, the overall size is still relatively moderate, which may not significantly hinder permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of ethoxy and methyl groups, which are non-polar. Additionally, the presence of hydrogen bond acceptors, such as the nitrogen atoms in the pyridine and pyrrolopyridine rings, may contribute to some degree of polarity. However, the overall polarity is balanced by the non-polar groups, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, as it does not contain any charged functional groups. This neutrality is favorable for permeability, as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings in the molecule contribute to a degree of rigidity, which can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings, including the pyridine and phenyl groups, can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The presence of non-polar groups and aromatic rings suggests that the molecule has a relatively low hydration energy, which can facilitate its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases of the membrane.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 245

**SMILES:** CCOC(=O)C1=CC=C(C=C1)NC(=O)N2CC3=C(C[C@H]2C4=NC(=NO4)C(C)C)N=CN3

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzoyl group and the triazole ring, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the specific arrangement of functional groups and rings might allow for sufficient permeation.

3. **Polarity**: The molecule contains a polar ester group (ethyl ester) and a triazole ring, which can contribute to its overall polarity. The polar surface area and the number of hydrogen bond donors/acceptors are moderate, which suggests a balance between hydrophilic and lipophilic properties. This balance can favor moderate permeability.

4. **Charge**: The molecule is neutral, which is generally favorable for permeability as it can interact with both the aqueous and lipid phases of the membrane.

5. **Rigidity**: The presence of multiple aromatic rings and a triazole ring imparts a degree of rigidity to the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeation.

7. **Hydration Energy**: The balance of hydrophilic and hydrophobic groups suggests that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the membrane.

8. **Membrane Affinity**: The molecule's structure suggests a balanced affinity for both the aqueous and lipid phases, which is typically desirable for good permeability in PAMPA assays.

Overall, considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between hydrophilic and lipophilic interactions with the artificial membrane.

Final answer: Low-to-moderate permeability

------
# 246

**SMILES:** COC1=CC=C(C=C1)C2=NOC(=N2)[C@@H]3CC4=C(CN3C(=O)NC5CCCCC5)NC=N4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure with several functional groups and ring systems that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the methoxyphenyl group, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule contains multiple fused rings, including a triazolopyrazine system, which can increase its molecular weight and size. While larger molecules generally have lower permeability, the specific arrangement of these rings may allow for favorable interactions with the membrane.

3. **Polarity**: The methoxy group and the carboxamide moiety introduce some degree of polarity. However, the overall structure is dominated by the lipophilic aromatic and heterocyclic rings, which likely outweigh the polar contributions, supporting higher permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The fused ring system imparts a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing the number of conformational states that hinder permeation.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the carboxamide may reduce the hydration energy of the molecule, aiding in its permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions suggests that the molecule has a favorable affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its lipophilicity, aromaticity, and balanced polarity.

Final answer: High permeability

------
# 247

**SMILES:** C1=CC=C(C=C1)C2=CSC(=N2)NC(=O)C3=C(C=NC=C3)NS(=O)(=O)C4=C(C=C(C=C4)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the difluorophenyl and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings can help to stabilize interactions with the membrane, potentially offsetting this effect.

3. **Polarity**: The sulfonamide group introduces some polarity, which can affect the molecule's solubility and permeability. However, the overall lipophilicity due to the aromatic rings is likely to dominate.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily diffuse through the hydrophobic lipid bilayer without encountering significant electrostatic barriers.

5. **Rigidity**: The aromatic rings and the thiazole moiety contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility required for passage.

6. **Aromaticity**: The presence of multiple aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide, may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous phase and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both phases, which is generally favorable for permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its lipophilicity, aromaticity, and balanced polarity.

Final answer: High permeability

------
# 248

**SMILES:** CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)OC(C)(C)C)C4=CC=C(C=C4)Cl)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a tert-butyl ester group and a chlorophenyl moiety suggests that the molecule is relatively lipophilic. Lipophilic compounds tend to have higher permeability due to their ability to dissolve in lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, with multiple rings and heteroatoms. While size can be a limiting factor for permeability, the presence of a rigid, polycyclic structure may help the molecule to fit into the lipid bilayer more effectively.

3. **Polarity**: The molecule contains a low polar surface area due to the presence of multiple aromatic rings and a chlorophenyl group. This low polarity can enhance permeability as it allows the molecule to interact favorably with the hydrophobic environment of the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The polycyclic structure contributes to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility required for passage through the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is advantageous for permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 249

**SMILES:** C1=CC=C2C(=C1)C(=NC(=N2)C3=C(C=NC=C3)C#N)NC4=CC(=C(C=C4)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex aromatic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as pyridine and aniline derivatives, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the artificial membrane, which mimics a lipid bilayer.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heteroatoms may allow for some degree of flexibility, which can mitigate the negative effects of size.

3. **Polarity**: The molecule contains several nitrogen atoms, which contribute to its polarity. However, the overall polarity is balanced by the extensive aromatic system, which is hydrophobic. The presence of a fluorine atom on the aniline ring can also increase the lipophilicity and reduce polarity.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic nature of the molecule contributes to its lipophilicity and may enhance interactions with the lipid bilayer, aiding in permeability.

7. **Hydration Energy**: The presence of polar groups and aromatic rings suggests that the hydration energy of the molecule is moderate, which can influence its permeability by affecting its solubility and interaction with the aqueous phase.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural features that facilitate membrane interaction.

Final answer: High permeability

------
# 250

**SMILES:** CC1=CC(=C(C=C1Cl)OC)NC(=O)CSC2=NC=C(C(=O)N2)S(=O)(=O)C3=CC=C(C=C3)C(C)(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of a chloro and methoxy group on the phenyl ring, along with a tert-butyl group, suggests that the molecule has a significant degree of lipophilicity. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a pyrimidinyl group. While these features can contribute to rigidity, they may also increase the molecular weight, which could negatively impact permeability. However, the balance of these factors will determine the overall permeability.

3. **Polarity**: The sulfonamide group introduces some polarity, but the overall structure is dominated by hydrophobic groups, which suggests that the molecule is more lipophilic than polar. This could favor permeability through the lipid-rich artificial membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and pyrimidinyl group contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The presence of aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of hydrophobic groups and aromatic rings suggests that the molecule has a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 251

**SMILES:** CC1=C(C=C(C=C1)NC(=O)NC2=CC3=C(C=C2N4CCCCC4)N(C(=O)N3C)C)Cl

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chloro-substituted phenyl group and a methylpiperidine moiety suggests that the molecule has a significant degree of lipophilicity. These groups contribute to the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434.3 g/mol. While size is a limiting factor for permeability, the presence of aromatic and heterocyclic rings can help to maintain a balance between size and permeability due to their planar nature, which can facilitate passage through the membrane.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of non-polar groups like the chloro-phenyl and methylpiperidine. Additionally, the urea linkage and the benzimidazole ring contribute to a moderate degree of polarity. However, the overall structure suggests that the molecule is more lipophilic than polar, which is favorable for permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The benzimidazole and piperidine rings introduce rigidity to the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings present in the structure, such as the phenyl and benzimidazole rings, can interact with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, facilitating its passage through the lipid-rich environment of the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it has a favorable membrane affinity, allowing it to interact with both the aqueous and lipid phases of the membrane.

Overall, the given molecule exhibits a combination of lipophilicity, rigidity, and balanced polarity that suggests it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 252

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=CC=CC=C2C(=O)NC3=NC(=C(S3)C)C4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole groups, contributes to the lipophilic nature of the molecule. This suggests that the given molecule may have a relatively high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule has a moderate molecular size and weight, as indicated by the presence of multiple aromatic rings and a sulfonamide group. While larger molecules can have issues with permeability, the balance of aromatic and non-aromatic components suggests it may still have sufficient permeability.

3. **Polarity**: The sulfonamide group introduces some polarity, but the overall structure is dominated by aromatic rings, which are hydrophobic. This suggests that the given molecule has a low polar surface area, which is associated with higher permeability.

4. **Charge**: The given molecule is neutral, which is typical for many drug molecules. This neutrality allows it to diffuse more easily through the lipid bilayer of the artificial membrane.

5. **Rigidity**: The aromatic rings and thiazole moiety contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The aromatic and hydrophobic nature of the given molecule suggests that it has a lower hydration energy, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 253

**SMILES:** CN(C)C(=O)C1=NC(=C2N1C=CN=C2)C3=C(C=C(C=C3)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the dichlorophenyl group contributes significantly to the lipophilicity of the molecule. Chlorine atoms increase the hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings and the imidazo[1,2-a]pyrazine core can help in maintaining a balance between size and permeability.

3. **Polarity**: The dichlorophenyl group and the imidazo[1,2-a]pyrazine core contribute to the molecule's overall hydrophobicity, reducing its polar surface area. This decrease in polarity can enhance permeability as it allows the molecule to interact more favorably with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without encountering significant electrostatic barriers.

5. **Rigidity**: The aromatic rings and the imidazo[1,2-a]pyrazine core provide a rigid structure, which can facilitate passage through the membrane by reducing the flexibility required for the molecule to fit into the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability by stabilizing the interaction with the membrane.

7. **Hydration Energy**: The low hydration energy of the given molecule suggests that it is less tightly bound to water molecules, which can improve its ability to permeate the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

------
# 254

**SMILES:** CC1=CC=CC=C1C2=NC3=CC=CC=C3C(=N2)NCC4=CC=C(C=C4)C5=CN=CC=C5

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a quinazoline derivative with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The quinazoline core and the attached aromatic rings suggest a relatively large molecular size. While size is a factor in permeability, the presence of multiple aromatic rings may still allow for sufficient permeation due to their planar nature, which can facilitate passage through the membrane.

3. **Polarity**: The pyridine and phenyl groups contribute to the overall polarity of the molecule. However, the presence of these groups is balanced by the non-polar characteristics of the aromatic rings, resulting in a moderate polar surface area. This balance can favor moderate permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The quinazoline core and the aromatic rings impart a degree of rigidity to the molecule. This rigidity can enhance its ability to permeate the membrane by reducing the flexibility required for passage.

6. **Aromaticity**: The aromatic nature of the molecule can influence its interaction with the lipid bilayer, potentially enhancing its permeability through hydrophobic interactions.

7. **Hydration Energy**: The balance of polar and non-polar regions in the molecule suggests that it may have a moderate hydration energy, which can influence its permeability by affecting the energy required to remove water molecules from the surface of the molecule.

8. **Membrane Affinity**: The structural features of the given molecule suggest a balanced affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and structural rigidity.

Final answer: Moderate permeability.

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# 255

**SMILES:** C1CN(CCC1C(=O)N)C2=NC(=CS2)C3=CC4=C(C=C3)OC=CC4=O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperidinecarboxamide, which is a type of compound that includes a piperidine ring attached to a carboxamide group. Let's analyze its properties to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of a chromen-4-one moiety, which is a heterocyclic aromatic compound, suggests that the given molecule has a degree of lipophilicity. This aromatic system can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The piperidine ring and the attached chromen-4-one moiety contribute to a relatively moderate molecular size. While larger molecules can have issues with permeability due to size constraints, the given molecule's size is likely manageable for passage through the membrane.

3. **Polarity**: The piperidine ring and the carboxamide group introduce some polar characteristics to the molecule. However, the overall structure is balanced with aromatic and non-polar components, which may allow it to maintain a moderate polar surface area. This balance can favor permeability as it allows the molecule to interact with both the aqueous and lipid phases.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their inability to interact with the hydrophobic environment.

5. **Rigidity**: The aromatic chromen-4-one moiety contributes to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation while interacting with the membrane.

6. **Aromaticity**: The presence of aromatic rings, such as the chromen-4-one and the piperidine ring, can influence the molecule's lipophilicity and its ability to interact with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The balance of polar and non-polar regions in the given molecule suggests that it may have a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The combination of lipophilic and polar characteristics in the given molecule suggests that it has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability in the PAMPA assay.

Overall, considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, neutral charge, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 256

**SMILES:** CCC1=C(C=C(C=C1)NC(=O)C2=C(C(=C(N2)C)C(=O)C)C)[S+](=O)(NC3=CC=CC(=C3)C#N)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The given molecule contains several aromatic rings and an acetyl group, which contribute to its lipophilic nature. This suggests that the molecule may have a high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The presence of multiple aromatic rings and a relatively complex structure indicates that the molecule is not extremely small, which might limit its permeability due to size constraints. However, the balance of these features suggests it may still have sufficient permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and acetyl groups, which are non-polar. This low polar surface area is associated with higher permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged species typically have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility required for passage through the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The given molecule likely has a lower hydration energy due to its aromatic and acetyl groups, which can reduce its affinity for water and enhance its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and structural features that favor interaction with the lipid bilayer.

Final answer: High permeability

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# 257

**SMILES:** CCOC(=O)C1=NN=C(S1)N[S+](=O)(C2=CC=C(C=C2)NC(=O)CC3=CC(=C(C=C3)Cl)Cl)[O-]

**Label:** 0

**Predi:** 0

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the dichlorophenyl group, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains several polar groups, including the sulfonamide and ester functionalities. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but could also hinder permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The presence of aromatic rings and the thiadiazole moiety contribute to the rigidity of the molecule. This rigidity can facilitate permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability. However, this effect can be balanced by the size and polarity of the molecule.

7. **Hydration Energy**: The molecule's structure suggests a moderate hydration energy, which can influence its ability to permeate the membrane. Lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous and lipid phases, which can be beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilic and polar characteristics, along with its structural rigidity and aromaticity, suggests that while it may have some difficulty permeating the membrane, it should still exhibit reasonable passage through the artificial lipid bilayer.

Final answer: Low-to-moderate permeability

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# 258

**SMILES:** CN1C=C(C=C1C(=O)NC2=CC(=C(C=C2)Cl)C(F)(F)F)S(=O)(=O)N3CCCCCC3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chloro and trifluoromethyl group on the phenyl ring increases the lipophilicity of the molecule. These groups are known to enhance the hydrophobic character, which can improve membrane permeability up to a certain point.

2. **Molecular Size and Weight**: The molecule contains a pyrrole ring and a sulfonyl group attached to a piperidine ring. The overall size and weight of the molecule are moderate, which suggests that while it may not be the smallest molecule, it is not excessively large either. This balance can favor moderate permeability.

3. **Polarity**: The molecule has a carboxamide group, which contributes to its polarity. However, the overall polar surface area is relatively low due to the presence of the lipophilic phenyl and trifluoromethyl groups. This balance of polar and non-polar regions can enhance permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic phenyl ring and the pyrrole ring contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings in the structure can interact with the lipid bilayer through π-π interactions, which can influence permeability.

7. **Hydration Energy**: The presence of polar groups like the sulfonyl and carboxamide can lead to moderate hydration energy, which may affect the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable interactions with the lipid bilayer.

Final answer: High permeability

------
# 259

**SMILES:** CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple chlorophenyl groups contributes to the lipophilic nature of the molecule. Chlorine atoms increase the electron density and hydrophobicity, enhancing the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The overall size of the molecule is moderate, with several aromatic rings and a pyrazole core. While the size is not excessively large, it may still pose some limitations for permeability due to steric hindrance.

3. **Polarity**: The molecule has a low polar surface area due to the dominance of hydrophobic aromatic rings over polar functional groups. This suggests that the molecule is likely to have a high permeability as it can traverse the hydrophobic environment of the artificial membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The pyrazole ring and aromatic systems contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The presence of multiple aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, which can aid in its permeation through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule exhibits a combination of lipophilicity, rigidity, and balanced polarity that suggests it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 260

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=CN=C2)C(=O)NCC3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of a benzyl group and a sulfonamide moiety suggests that the given molecule has a significant lipophilic character. This is because benzyl groups are hydrophobic, and sulfonamides can contribute to lipophilicity due to their aromatic nature.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a sulfonamide group. This complexity can lead to a moderate molecular size, which may affect its permeability. Larger molecules often have lower permeability due to reduced ability to pass through the membrane.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by hydrophobic aromatic rings, which suggests that the molecule is more lipophilic than polar.

4. **Charge**: The given molecule is neutral, which is typical for many drug molecules. This neutrality allows it to interact favorably with the lipid bilayer of the artificial membrane, enhancing its permeability.

5. **Rigidity**: The presence of multiple aromatic rings contributes to the rigidity of the molecule. Rigidity can improve membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The aromatic rings in the given molecule can enhance its lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of aromatic and hydrophobic groups suggests that the given molecule has a lower hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

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# 261

**SMILES:** CC1=C(N(C(=C1C(=O)C)C)C)C(=O)NC2=CC(=C(C=C2)OC)[S+](=O)(NC3=CC=C(C=C3)Br)[O-]

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with multiple functional groups that can influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the acetylphenyl and methoxyphenyl groups, contributes to the lipophilicity of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule contains a pyrrole ring and several substituents, which may contribute to a moderate molecular size. While the aromatic and heterocyclic components can increase the molecular weight, the overall size is balanced by the smaller substituents, which may still allow for sufficient permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and the methoxy group, which can reduce hydrogen bonding interactions with the aqueous environment. This characteristic can enhance its ability to permeate the lipid-rich artificial membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings and the pyrrole core contribute to a relatively rigid structure, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Hydration Energy**: The presence of methoxy and acetyl groups may lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing the energy required to displace water molecules.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule's structural features, such as its aromaticity, moderate size, and balanced polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 262

**SMILES:** C1CCN(C1)C2=C(C=C(C=C2)NC3=NC(=NC4=CC=CC=C43)C5=CC=NC=C5)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and quinazoline rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may allow for some flexibility in fitting through the membrane.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to polarity. However, the overall structure is dominated by aromatic systems, which are less polar. The pyridine and quinazoline rings, along with the pyrrolidine group, suggest a balance between hydrophobic and hydrophilic interactions, which can be favorable for membrane permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and heterocycles contribute to a rigid structure, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of multiple aromatic systems can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups suggests that the molecule may have a moderate hydration energy, which can influence its ability to permeate the membrane.

8. **Membrane Affinity**: The combination of lipophilic and polar features suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is often desirable for good permeability.

Overall, the given molecule's structural features, such as its aromaticity, balance of hydrophobic and hydrophilic groups, and neutral charge, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 263

**SMILES:** CNC1=C(C=CC(=N1)C2=CC=CC3=CC=CC=C32)C#N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a phenanthridine derivative with a nitrile group attached to the pyridine ring. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of the phenanthridine moiety, which is a polycyclic aromatic hydrocarbon, contributes to the lipophilicity of the molecule. This aromatic system can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The given molecule is relatively small, which is beneficial for permeability. Smaller molecules generally have an easier time crossing biological membranes due to less steric hindrance.

3. **Polarity**: The pyridine ring introduces some polarity, but the overall structure is dominated by the lipophilic phenanthridine and nitrile groups. The presence of a nitrile group can also contribute to polarity, but its linear nature may not significantly hinder permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings in the phenanthridine and pyridine structures contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the phenanthridine and pyridine rings can facilitate interactions with the lipid bilayer, potentially increasing permeability through π-π interactions or van der Waals forces.

7. **Hydration Energy**: The nitrile group and aromatic rings may lower the hydration energy of the molecule, making it easier for the molecule to traverse the aqueous environment surrounding the membrane and interact with the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule's structural features, including its aromaticity, rigidity, and balance of lipophilic and polar characteristics, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 264

**SMILES:** CC1=CC=C(C=C1)C(=O)N2CCN(CC2)C3=NC=CC(=N3)NC4=CC=CC=C4OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the methoxyphenyl and pyrimidinyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of multiple aromatic rings and heterocycles may help to maintain a balance, allowing for sufficient permeability despite the size.

3. **Polarity**: The methoxy group and the piperazine ring introduce some degree of polarity to the molecule. However, the overall structure is dominated by aromatic and heterocyclic components, which are generally more lipophilic. This suggests that the molecule may have moderate polarity, which can influence its interaction with the membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to fit into the membrane's lipid bilayer, potentially improving its permeability.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the lipid bilayer, which may enhance its permeability.

7. **Hydration Energy**: The presence of multiple aromatic and heterocyclic rings suggests that the molecule may have a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is advantageous for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 265

**SMILES:** C1CC2=C(C1)SC3=NC=NC(=C23)NC(=O)C4=CC=CO4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound that includes a furan ring and a tricyclic system containing sulfur and nitrogen atoms. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of the furan ring, which is aromatic and relatively non-polar, contributes to the lipophilicity of the molecule. Additionally, the tricyclic system with sulfur and nitrogen atoms may also enhance lipophilicity due to its rigid and planar structure. This suggests that the molecule is likely to have a moderate to high lipophilicity.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings can help to stabilize the molecule within the membrane, potentially offsetting some of this effect.

3. **Polarity**: The molecule contains polar functional groups, such as the amide linkage, which can form hydrogen bonds. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting that the molecule has a moderate polar surface area.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without being repelled by charges.

5. **Rigidity**: The tricyclic system provides a rigid structure, which can enhance the molecule's ability to permeate the membrane by reducing its flexibility and allowing it to fit more snugly into the lipid bilayer.

6. **Aromaticity**: The aromatic rings in the molecule can interact with the lipid bilayer through π-π interactions, which can enhance its permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility in water and lipid phases.

8. **Membrane Affinity**: The balance of lipophilic and polar characteristics suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Overall, considering these properties, the given molecule is likely to exhibit high permeability in the artificial membrane used in the PAMPA assay.

Final answer: High permeability

------
# 266

**SMILES:** C1CN(CCC1C(=O)N)C2=NC(=CS2)C3=CC=CC=C3C(F)(F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperidinecarboxamide, which is a type of compound known for its potential biological activity. Let's analyze its structural features to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of a trifluoromethyl group attached to a phenyl ring increases the lipophilicity of the molecule. This group is known for enhancing the hydrophobic character, which can improve membrane permeability up to a certain extent.

2. **Molecular Size and Weight**: The molecule contains a thiazole ring and a piperidine ring, which contribute to its overall size. While the piperidine ring is relatively small, the thiazole ring and the trifluoromethyl group add to the molecular weight. Generally, larger molecules have lower permeability, but the specific arrangement and functional groups can influence this.

3. **Polarity**: The piperidine ring and the carboxamide group introduce some degree of polarity. However, the overall polarity is balanced by the lipophilic trifluoromethyl group, which may not significantly hinder permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The thiazole ring contributes to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The phenyl ring is aromatic, which can influence lipophilicity and interactions with the lipid bilayer. Aromatic rings can engage in π-π interactions with the membrane, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups like the carboxamide may reduce the hydration energy, facilitating membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable structural features for membrane interaction.

Final answer: High permeability

------
# 267

**SMILES:** CN1C=CC2=C(N=C(C=C21)C3=CC=CC=C3C#N)C(=O)NCC4=CN=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a cyano group and aromatic rings, such as the pyrrolo[3,2-b]pyridine and pyridine rings, contribute to the lipophilic nature of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a limiting factor for permeability, the presence of aromatic rings and a rigid structure may help the molecule to permeate the membrane more efficiently compared to smaller, more flexible molecules.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the low number of hydrogen bond donors and acceptors. This low polarity suggests that the molecule has a high degree of lipophilicity, which is favorable for permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the pyrrolo[3,2-b]pyridine core contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of aromatic rings can influence the molecule's interaction with the lipid bilayer, potentially enhancing its permeability due to favorable hydrophobic interactions.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it can easily interact with the lipid bilayer, facilitating its permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 268

**SMILES:** CC1=C(C(=CC=C1)C)NC(=O)C2=NC(=NC=C2Cl)SC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a pyrimidinecarboxamide with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chloro group and a methylthio group on the pyrimidine ring increases the lipophilicity of the molecule. These groups can enhance the molecule's ability to interact with the hydrophobic environment of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively compact, with a moderate molecular weight. This compactness can contribute to higher permeability as it allows the molecule to fit through the membrane more easily compared to larger, bulkier molecules.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar substituents like the chloro and methylthio groups. This low polarity can enhance its ability to traverse the lipid bilayer, as it reduces the energy required for the molecule to transition from an aqueous to a lipid environment.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid membranes due to their interaction with the polar head groups of the membrane lipids.

5. **Rigidity**: The pyrimidine ring provides a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent orientation and reducing the likelihood of entropic barriers.

6. **Aromaticity**: The presence of aromatic rings, such as the pyrimidine and phenyl groups, can enhance lipophilicity and facilitate interactions with the lipid bilayer through π-π interactions. This can contribute to the molecule's ability to permeate the membrane.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less tightly bound to water molecules, which can enhance its ability to permeate the membrane by reducing the energy required to release water molecules upon crossing the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases of the membrane.

Overall, the given molecule exhibits a combination of lipophilic, neutral, and rigid characteristics that favor high permeability in the PAMPA assay.

Final answer: High permeability

------
# 269

**SMILES:** CC1=CC(=C(C(=O)N1)CNC(=O)C2=C3C=CNC3=CC(=N2)C4=C(N=CC=C4)OC)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and indole moieties, contributes to the lipophilic character of the molecule. This suggests that the molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and a complex structure, which may limit its permeability due to size constraints. Larger molecules often have reduced permeability as they may face steric hindrance in passing through the artificial membrane.

3. **Polarity**: The molecule contains multiple nitrogen atoms, which can contribute to its polarity. However, the overall polarity is balanced by the aromatic rings and the presence of a carbonyl group, which may not significantly hinder permeability but also does not enhance it excessively.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The indole and pyridine rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent conformation.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the membrane, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups and aromatic rings suggests that the molecule may have moderate hydration energy, which can influence its interaction with the aqueous and lipid phases, potentially aiding in permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a favorable membrane affinity, aiding in its permeability.

Overall, considering these structural features, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay.

Final answer: High permeability

------
# 270

**SMILES:** CCCCOC1=CC=C(C=C1)C(=O)N2CCC(CC2)C3=NNC(=O)N3C4=CC=C(C=C4)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a butoxy group and a methylphenyl group suggests that the molecule has a significant degree of lipophilicity. These groups contribute to the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434. This size can affect permeability, as larger molecules may have reduced permeability due to steric hindrance and difficulty in navigating the membrane. However, the specific arrangement of functional groups and rings can mitigate this effect.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the few polar functional groups present. The polar surface area is relatively low due to the dominance of hydrophobic groups, which can enhance permeability by reducing interactions with the aqueous environment and increasing interactions with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with polar head groups of the membrane.

5. **Rigidity**: The triazolone ring and the aromatic phenyl rings contribute to the rigidity of the molecule. Rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl groups, can influence lipophilicity and membrane interactions. Aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy suggests that the molecule is less likely to form strong interactions with water, which can facilitate its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 271

**SMILES:** CN1CCN(CC1)C2=NC=CC(=C2)C3=NC4=CC=CC=C4C(=N3)NC5=CC(=C(C=C5)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of the difluorophenyl group and the quinazoline moiety contribute to the lipophilic nature of the molecule. These aromatic and halogenated groups enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The overall size of the molecule, including the piperazine and quinazoline rings, is relatively large. While size is a factor in permeability, the presence of multiple aromatic rings and the difluorophenyl group may still allow for sufficient permeation through the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic rings and the presence of fluorine atoms, which are less polar than other substituents. This low polarity contributes to higher permeability as it allows the molecule to interact favorably with the hydrophobic environment of the membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings and the quinazoline core provide a rigid structure, which can facilitate passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The aromatic rings, including the phenyl and quinazoline groups, enhance lipophilicity and may also participate in π-π interactions with the membrane, further aiding in permeability.

7. **Hydration Energy**: The presence of fluorine atoms and the overall structure suggest a lower hydration energy, which can improve the molecule's ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a favorable membrane affinity, which is essential for high permeability in the PAMPA assay.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and balanced polarity.

Final answer: High permeability

------
# 272

**SMILES:** CN(C)C1=CC=CC(=C1)C2=CN=C(C3=C2CCO3)NC4=CN=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 342.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heterocycles may allow for some flexibility in permeation, but it might limit permeability compared to smaller molecules.

3. **Polarity**: The molecule has a low polar surface area, which is due to the presence of aromatic rings and the absence of highly polar functional groups. This contributes to its lipophilicity and can enhance permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and heterocycles introduces rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is not strongly bound to water, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilicity, rigidity, and balanced polarity that suggests it would have high permeability in the PAMPA assay.

Final answer: High permeability

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# 273

**SMILES:** CCOC(=O)C1=C(SC2=C1CCN(C2)C(=O)OCC)NC(=O)CN3CCCCC3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple ethyl groups and the thieno[3,2-c]pyridine core contribute to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434.4 g/mol. While size is a factor in permeability, the presence of multiple rings and functional groups may allow for some flexibility, potentially mitigating the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the low number of hydrogen bond donors and acceptors. This low polarity suggests that the molecule can interact favorably with the hydrophobic environment of the artificial membrane, enhancing permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The thieno[3,2-c]pyridine core provides a degree of rigidity, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic thieno[3,2-c]pyridine ring system can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it can easily transition from an aqueous environment to a lipid environment, enhancing its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for membrane permeation.

Overall, the given molecule exhibits several structural features that suggest it would have high permeability in the PAMPA assay, owing to its lipophilicity, neutral charge, low polarity, and favorable membrane interactions.

Final answer: High permeability

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# 274

**SMILES:** CC1=C(C(=CC=C1)C)C(=O)NC2=CC(=C(C=C2)OC)[S+](=O)(NC3=CC=C(C=C3)Br)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a benzamide derivative, which is a class of compounds known for their potential biological activity. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the bromophenyl and methoxyphenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high degree of lipophilicity.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple aromatic rings and substituents, which may increase its molecular weight. However, the presence of smaller substituents like the methoxy and methyl groups can help balance this effect, potentially allowing for moderate permeability.

3. **Polarity**: The molecule contains polar functional groups such as the amide linkage and the methoxy group. These groups can form hydrogen bonds, which may influence the molecule's interaction with the polar head groups of the artificial membrane. However, the overall polarity is balanced by the extensive aromatic system, suggesting moderate polarity.

4. **Charge**: The given molecule is neutral, which is typical for benzamide derivatives. This neutrality allows the molecule to traverse the lipid bilayer more effectively compared to charged molecules.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, enhancing permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it may have moderate hydration energy, which can influence its permeability by affecting the energy required to remove water molecules from the surface of the molecule.

8. **Membrane Affinity**: The given molecule's structure suggests a balanced affinity for both the aqueous phase and the lipid bilayer, which is often desirable for good permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 275

**SMILES:** C[C@H]1C/C=C/C2[C@@H](C(=C)[C@H](C3[C@@]2([C@H](/C=C/[C@](C1)(C)O)OC(=O)C)C(=O)N[C@H]3CC4=CC=CC=C4)C)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methyl groups and a benzyl group suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular framework, which includes a tricyclic structure. While size can be a limiting factor for permeability, the specific arrangement of rings and substituents may allow for sufficient flexibility and conformational adaptability to traverse the membrane.

3. **Polarity**: The molecule contains a hydroxy group and an acetate ester, which contribute to its polarity. However, the overall polarity is balanced by the lipophilic benzyl and methyl groups, suggesting moderate polarity. This balance can favor permeability, as it allows the molecule to interact with both the aqueous and lipid phases.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The tricyclic structure imparts a degree of rigidity to the molecule. While rigidity can sometimes hinder permeability due to limited conformational flexibility, the specific arrangement of the rings and substituents may still allow for sufficient membrane interaction.

6. **Aromaticity**: The presence of an aromatic benzyl group can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of hydroxy and ester groups suggests that the molecule may have moderate hydration energy, which can influence its solubility and permeability. Lower hydration energy can enhance membrane permeation.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic groups in the given molecule suggests that it has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, neutral charge, and favorable structural characteristics for membrane interaction.

Final answer: High permeability

------
# 276

**SMILES:** C1=CC=C(C=C1)CNC2=NC(=NC3=CC=CC=C32)NCC4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of quinazoline, which is a bicyclic compound consisting of a benzene ring fused to a pyrimidine ring. This core structure is known for its planar and aromatic nature, which can influence the molecule's interaction with the lipid bilayer in the PAMPA assay.

The presence of the quinazoline core contributes to the molecule's lipophilicity, enhancing its ability to permeate the hydrophobic environment of the artificial membrane. This is because aromatic systems can engage in π-π interactions with the lipid bilayer, facilitating passage through the membrane.

Additionally, the molecule contains benzyl groups attached to the nitrogen atoms. These benzyl groups further increase the lipophilicity of the molecule, as they are hydrophobic and can enhance the overall non-polar character of the compound. This increased lipophilicity generally correlates with higher permeability in PAMPA assays.

The molecule is also described as having a low polar surface area and few hydrogen bond donors or acceptors. This low polarity suggests that the molecule has limited interactions with water, which can hinder its solubility in aqueous environments but favor its passage through the lipid-rich membrane.

The charge of the molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid bilayers due to their interaction with polar head groups of lipids.

Overall, the given molecule's structural features, including its aromatic quinazoline core, benzyl substituents, low polarity, and neutral charge, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 277

**SMILES:** CC1=C(C(C(=C(N1)C)C(=O)OCCCN2CCC(CC2)(C3=CC=CC=C3)C4=CC=CC=C4)C5=CC(=CC=C5)[N+](=O)[O-])C(=O)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl groups and the piperazine ring, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic and cyclic structures may help to maintain a balance, potentially allowing for moderate permeability.

3. **Polarity**: The molecule contains several polar groups, including nitro groups and ester linkages. However, the overall polar surface area is balanced by the extensive aromatic and alkyl regions, which may reduce the overall polarity. This balance suggests that the molecule might have moderate polarity, which could impact its permeability.

4. **Charge**: The molecule is neutral, as it is not an ionized species. This neutrality is favorable for permeability, as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and the piperazine ring contributes to a degree of rigidity in the molecular structure. This rigidity can enhance the ability of the molecule to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability. However, the presence of multiple rings might also lead to steric hindrance, potentially limiting permeability.

7. **Hydration Energy**: The molecule's structure, with its balance of hydrophobic and hydrophilic regions, suggests that it may have a moderate hydration energy. This can influence its ability to permeate the membrane, as lower hydration energy generally facilitates membrane passage.

8. **Membrane Affinity**: The given molecule appears to have a balanced affinity for both the aqueous phase and the lipid bilayer, as indicated by its structural features. This balance is crucial for optimal permeability in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity, which facilitate its interaction with the artificial membrane.

Final answer: High permeability

------
# 278

**SMILES:** C1=CC=C2C(=C1)/C(=C/C3=CC=CN3)/C(=O)N2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Indole Core**: The presence of an indole moiety is significant. Indole is a bicyclic structure that includes a benzene ring fused to a pyrrole ring. This structure is known for its aromaticity and ability to participate in π-π interactions, which can enhance lipophilicity and membrane affinity. The indole core is often associated with good permeability due to its planar structure and ability to interact with lipid bilayers.

2. **Pyrrole Moiety**: The pyrrole ring is a five-membered heterocycle containing nitrogen. Pyrrole is relatively polar compared to benzene, but in this context, it is part of a conjugated system with the indole, which may enhance the overall lipophilicity of the molecule. The presence of the pyrrole ring can also contribute to the molecule's ability to form hydrogen bonds, which may affect its interaction with the membrane.

3. **Conjugated System**: The given molecule has a conjugated system involving the pyrrole and indole rings. This conjugation can enhance the molecule's ability to interact with the lipid bilayer, potentially increasing its permeability. Conjugated systems often have increased stability and can participate in electron delocalization, which may facilitate passage through the membrane.

4. **Z-Isomer Configuration**: The Z-configuration of the double bond between the pyrrole and indole rings suggests a specific spatial arrangement that may influence the molecule's ability to fit into the membrane. This configuration can affect the overall shape and flexibility of the molecule, which are important factors in membrane permeability.

5. **Lipophilicity and Polarity**: The combination of aromatic rings and heterocycles suggests that the given molecule has a balance of lipophilic and polar characteristics. This balance is crucial for membrane permeability, as it allows the molecule to interact with both the hydrophobic core and the hydrophilic exterior of the lipid bilayer.

6. **Charge and Rigidity**: The given molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid membranes. Additionally, the rigidity imparted by the aromatic and heterocyclic rings can enhance the molecule's ability to permeate the membrane by reducing its flexibility and conformational changes.

Overall, the given molecule's structural features, including its aromaticity, conjugation, and balance of lipophilic and polar characteristics, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 279

**SMILES:** CC1=NN(C2=C1C(=CC(=O)N2)C(F)(F)F)CCC3=NC(=CS3)C4=CC=C(C=C4)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a methoxyphenyl group and a trifluoromethyl group contributes to the lipophilic nature of the molecule. These groups increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and a considerable molecular weight. While size can be a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help to maintain a balance by providing rigidity and planarity, which can facilitate passage through the membrane.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the few polar functional groups present. The methoxy group and the pyrazolo-pyrimidinone core contribute to this characteristic, which is favorable for permeability as it reduces the molecule's affinity for water and enhances its interaction with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes due to their interaction with polar head groups of the membrane.

5. **Rigidity**: The pyrazolo-pyrimidinone core and the aromatic rings contribute to the rigidity of the molecule. This rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings present in the structure can interact with the lipid bilayer through π-π interactions, which can enhance permeability. Additionally, these rings contribute to the overall lipophilicity of the molecule.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, which can facilitate its passage through the hydrophobic environment of the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is essential for high permeability in the PAMPA assay.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, rigidity, and balanced polarity.

Final answer: High permeability

------
# 280

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=CN=C2)C(=O)NC3=NC(=CS3)C4CCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the provided properties.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine rings, contributes to the lipophilic nature of the molecule. This suggests that the given molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule contains several heterocyclic rings, including a thiazole and a pyridine ring, which contribute to its molecular complexity. While these rings can increase the molecular weight, the overall size and weight are balanced by the relatively small cyclopentyl group, suggesting that the molecule is not excessively large, which is beneficial for permeability.

3. **Polarity**: The sulfonamide group is polar, but the overall polar surface area is balanced by the lipophilic aromatic rings. The presence of a low number of hydrogen bond donors and acceptors indicates that the molecule has a relatively low polarity, which can enhance permeability.

4. **Charge**: The given molecule is neutral, which is typical for many drug molecules. This neutrality allows it to diffuse more easily through the lipid bilayer of the artificial membrane.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings contributes to the rigidity of the molecule. This rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The balance of polar and nonpolar regions in the molecule suggests that it may have a moderate hydration energy, which can influence its ability to permeate the membrane.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is indicative of good membrane permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate molecular size, low polarity, and neutral charge.

Final answer: High permeability

------
# 281

**SMILES:** CC1=C(C(=CC=C1)C)N[S+](=O)(C2=CC=CC(=C2)NC(=O)C3=C(C(=C(N3)C)C(=O)C)C)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and acetylphenyl groups, contributes to the lipophilic nature of the molecule. These rings can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule contains multiple aromatic rings and a pyrrole ring, which contribute to its overall size and weight. While larger molecules can have lower permeability due to size constraints, the aromatic nature may still allow for sufficient permeability.

3. **Polarity**: The molecule has a carboxamide group, which introduces some polarity. However, the overall structure is dominated by the lipophilic aromatic rings, suggesting that the molecule's polarity is not high enough to significantly hinder its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the pyrrole core contribute to a rigid structure, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The aromatic and amide groups may lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing the energy required to remove water molecules.

8. **Membrane Affinity**: The balance of hydrophobic aromatic groups and the polar amide group suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability.

Overall, the given molecule's structure, with its aromatic rings, amide linkage, and moderate size, suggests that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 282

**SMILES:** CC1=C(NC(=C1C(=O)C)C)C(=O)NC2=CC(=CC=C2)S(=O)(=O)NC3=CC=CC=C3OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex aromatic amide with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Aromaticity and Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyrrole rings, contributes to the lipophilicity of the molecule. Aromatic rings can enhance the ability of the molecule to interact with the lipid bilayer, potentially increasing its permeability.

2. **Amide Linkage**: The amide group is a polar functional group, but in this molecule, it is part of a larger structure that includes aromatic rings, which can moderate its polarity. Amides can form hydrogen bonds, which may aid in interactions with the membrane, but the overall effect on permeability will depend on the balance with other structural features.

3. **Acetyl Groups**: The acetyl groups present in the molecule add to its lipophilicity and may enhance membrane permeability by increasing the hydrophobic character of the molecule.

4. **Methoxy Group**: The methoxy group is an electron-donating group that can increase the lipophilicity of the molecule. It may also participate in weak interactions with the membrane, potentially aiding in permeability.

5. **Methyl Substituents**: The presence of methyl groups on the pyrrole ring increases the hydrophobic character of the molecule, which can enhance its ability to permeate the lipid bilayer.

6. **Overall Molecular Size and Polarity**: The given molecule is relatively large and has a moderate polar surface area due to the amide and methoxy groups. However, the presence of multiple aromatic rings and acetyl groups suggests that the molecule's overall lipophilicity is higher than its polarity.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and moderate polar surface area. The balance between hydrophobic and hydrophilic interactions with the artificial membrane likely favors permeability.

Final answer: High permeability

------
# 283

**SMILES:** C1CC2=C(C(N=C(N2)NC3=NC4=C(O3)C(=CC=C4)Cl)C5=C(C=NN5)Cl)C(=O)C1

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including the chloro-substituted benzoxazole and the pyrimidine ring, suggests a significant degree of lipophilicity. This lipophilicity is likely to enhance the molecule's ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 344.3 g/mol. While size is a limiting factor for permeability, the presence of multiple rings and heteroatoms may create a rigid structure that could facilitate passage through the membrane.

3. **Polarity**: The molecule contains several nitrogen and oxygen atoms, contributing to its polar surface area. However, the overall polarity is balanced by the extensive aromatic system, which may reduce the molecule's solubility in water and enhance its interaction with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings suggests a high degree of rigidity, which can enhance the molecule's ability to permeate the membrane by reducing its flexibility and conformational changes.

6. **Aromaticity**: The aromatic rings, particularly the benzoxazole and pyrimidine, contribute to the molecule's lipophilicity and may facilitate interactions with the lipid bilayer through π-π stacking or hydrophobic interactions.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 284

**SMILES:** COC1=CC=CC=C1C2=NC3=CC=CC=C3C(=N2)NCC4=CC=C(C=C4)C5=CN=CC=C5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and phenyl groups, contributes to the lipophilic nature of the molecule. These rings can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular structure due to the presence of multiple aromatic rings and a quinazoline core. While size can be a limiting factor for permeability, the specific arrangement and connectivity of these rings may allow for sufficient flexibility and conformational adaptability to traverse the membrane.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to its polar character. However, the overall polar surface area is balanced by the extensive aromatic system, which is more lipophilic. This balance suggests moderate polarity, which is generally favorable for permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The quinazoline core provides a degree of rigidity to the molecule. While rigidity can sometimes hinder permeability due to limited conformational flexibility, in this case, it may help the molecule maintain a stable orientation when interacting with the membrane.

6. **Aromaticity**: The presence of multiple aromatic systems, including pyridine and phenyl rings, enhances the molecule's lipophilicity and may facilitate interactions with the lipid bilayer, promoting permeability.

7. **Hydration Energy**: The aromatic and heterocyclic components of the molecule likely have a lower hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a favorable membrane affinity, which is essential for high permeability in the PAMPA assay.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 285

**SMILES:** CNC1(CCCCC1=O)C2=CC=CC=C2Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a substituted cyclohexanone, which is a type of aryl ketone. Let's analyze its properties to predict its permeability in the PAMPA assay:

1. **Lipophilicity**: The presence of a 2-chlorophenyl group contributes to the lipophilic nature of the molecule. Chlorine atoms increase lipophilicity due to their electron-withdrawing nature, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The cyclohexanone core provides a relatively compact structure, which is beneficial for permeability. The overall molecular weight is moderate, and the size is not excessively large, which suggests that the molecule can traverse the membrane without significant steric hindrance.

3. **Polarity**: The molecule has a low polar surface area due to the presence of the chlorophenyl group and the cyclohexanone moiety. This low polarity aids in membrane permeability as it allows the molecule to interact favorably with the hydrophobic lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The cyclohexanone structure provides a certain degree of rigidity, which can enhance the molecule's ability to permeate the membrane by maintaining a consistent conformation that can interact effectively with the membrane.

6. **Aromaticity**: The presence of the aromatic phenyl ring can influence the molecule's interaction with the lipid bilayer, potentially enhancing its permeability through π-π interactions with the aromatic residues in the membrane.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which is beneficial for permeability as it indicates that the molecule can easily transition from an aqueous environment to a lipid environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is essential for its permeability in the PAMPA assay.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, and structural features that enhance its interaction with the artificial membrane.

Final answer: High permeability

------
# 286

**SMILES:** CCC(=O)NC(C1=CC=C(C=C1)OC)C2=CC(=C3C=CC=NC3=C2O)Cl

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a hydroxyquinoline derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chloro group and a methoxyphenyl group contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively complex, with a quinoline core and additional substituents. While the quinoline core is aromatic and planar, the presence of additional groups like the chloro and methoxyphenyl groups may increase the molecular weight and size, which could reduce permeability compared to smaller molecules.

3. **Polarity**: The hydroxyquinoline moiety introduces some polarity due to the hydroxyl group, which can form hydrogen bonds. However, the overall polarity is balanced by the lipophilic substituents, suggesting moderate polarity. This balance can favor moderate permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The quinoline core provides a degree of rigidity, which can facilitate passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The quinoline and methoxyphenyl groups contribute to the aromatic character, which can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups like the hydroxyl and amide groups can lead to moderate hydration energy, which may influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and polarity, and having a suitable size and rigidity for membrane passage.

Final answer: Low-to-moderate permeability

------
# 287

**SMILES:** CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=CN(C5=CC=CC=C54)CCCSC(=N)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of indole groups and the overall aromatic structure contribute to the lipophilicity of the molecule. Indole rings are known for their hydrophobic character, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting high permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with multiple aromatic rings and a carbamimidothioate group. While size can be a limiting factor for permeability, the presence of indole groups and the overall structure suggest that the molecule's size is balanced by its lipophilicity, potentially leading to moderate permeability.

3. **Polarity**: The molecule contains a low number of polar functional groups, such as the carbamimidothioate moiety. This low polar surface area can facilitate interaction with the hydrophobic environment of the artificial membrane, enhancing permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The indole and pyrrole rings contribute to the rigidity of the molecule. Rigidity can improve membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The indole and pyrrole rings provide aromatic character, which can enhance lipophilicity and facilitate interactions with the lipid bilayer, supporting high permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it can easily transition from an aqueous environment to a lipid environment, enhancing its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Overall, the given molecule's structural features, such as its lipophilicity, aromaticity, and rigidity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 288

**SMILES:** CC(=O)C1=CC=C(C=C1)C2=CSC(=N2)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring, which is a heterocyclic compound containing both sulfur and nitrogen, contributes to the molecule's aromaticity and potential for electronic interactions. This can enhance the molecule's lipophilicity, which is generally associated with increased permeability.

The molecule also contains an acetamidophenyl group, which is an aromatic ring with an amide substitution. This group can further contribute to the molecule's lipophilicity and may also participate in specific interactions with the artificial membrane, such as π-π stacking or hydrogen bonding.

Overall, the combination of these structural features suggests that the given molecule likely has a moderate to high permeability in the PAMPA assay, due to its balance of lipophilicity, aromaticity, and potential for specific interactions with the membrane.

Final answer: High permeability

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# 289

**SMILES:** CC1=CC=CC=C1N[S+](=O)(C2=CC=CC(=C2)NC(=O)C3=C(C(=C(N3)C)C(=O)C)C)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyrrole rings, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule contains multiple aromatic rings and a relatively large molecular structure, which may limit its permeability due to steric hindrance. However, the presence of smaller substituents like the acetyl and methyl groups can help balance this effect.

3. **Polarity**: The amide group introduces some polarity, but the overall structure is dominated by the lipophilic aromatic rings. This suggests that the molecule may have moderate polarity, which can influence its interaction with the membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation during passage.

6. **Aromaticity**: The aromatic nature of the molecule can facilitate interactions with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of both hydrophobic and hydrophilic regions in the molecule suggests that it may have a balanced hydration energy, which can aid in membrane permeation.

8. **Membrane Affinity**: The combination of lipophilic and polar characteristics suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Overall, the given molecule's structure, with its aromatic amide nature, suggests that it would exhibit high permeability in the artificial membrane assay.

Final answer: High permeability

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# 290

**SMILES:** C[C@H]1CN(C[C@@H]1C2=NC(=NO2)C3=CN=CC=C3)C(=O)C4=NN(C5=CC=CC=C54)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyridine and indazole moieties, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule contains a pyrrolidine ring, which is relatively small and contributes to the overall compact structure. This compactness can facilitate passage through the membrane, as larger molecules may face steric hindrance.

3. **Polarity**: The molecule has a low polar surface area due to the presence of multiple aromatic rings, which are non-polar. This characteristic can enhance its permeability by reducing interactions with the aqueous environment and increasing interactions with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with polar head groups of the membrane.

5. **Rigidity**: The indazole and pyridine rings contribute to the rigidity of the molecule. Rigidity can improve membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Hydration Energy**: The presence of aromatic and heterocyclic rings suggests that the molecule has a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to displace water molecules.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilicity, structural rigidity, and balanced polarity that suggests it would have high permeability in the PAMPA assay.

Final answer: High permeability

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# 291

**SMILES:** CCCCOC1=CC=C(C=C1)CNC(=O)C2=NN3CCCN(C(=O)C3=C2)CC4=CC=C(C=C4)C

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the butyl and methylphenoxy groups contributes to the lipophilic nature of the molecule. These groups increase the hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The structure includes a pyrazolo[1,5-a]pyrimidine core, which is relatively rigid and contributes to the overall molecular size. While the size of the molecule is moderate, the rigidity may help in maintaining a favorable orientation for permeation.

3. **Polarity**: The molecule has a carboxamide group, which introduces some polarity. However, the overall polar surface area is relatively low due to the dominance of hydrophobic groups, which may favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers.

5. **Rigidity**: The pyrazolo[1,5-a]pyrimidine core provides a rigid framework, which can enhance the ability of the molecule to interact with the lipid bilayer in a favorable orientation.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl group, can influence lipophilicity and membrane interactions, potentially enhancing permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups suggests that the molecule may have a lower hydration energy, facilitating membrane permeation.

8. **Membrane Affinity**: The combination of hydrophobic and polar groups suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is typically favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and polarity.

Final answer: High permeability

------
# 292

**SMILES:** COC1=CC(=CC(=C1OC)OC)C(=O)N2CCN(CC2)C3=C(C=CC(=C3)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay.

Firstly, the presence of the chlorophenyl group contributes to the lipophilicity of the molecule. Chlorine atoms increase the hydrophobic character of the phenyl ring, enhancing the molecule's ability to interact with the lipid components of the artificial membrane. This can lead to increased permeability.

Secondly, the trimethoxyphenyl group further increases the lipophilicity due to the presence of methoxy groups. These groups can enhance the molecule's ability to penetrate the lipid bilayer by increasing its overall hydrophobicity. However, the methoxy groups also introduce some degree of polarity, which can affect the balance between hydrophilicity and lipophilicity.

The piperazine ring in the molecule is a common motif in many pharmaceuticals and can influence the molecule's ability to permeate membranes. Piperazine rings are relatively flexible and can adopt various conformations, which may facilitate interaction with the membrane. However, the presence of nitrogen atoms in the piperazine ring can also introduce some polarity, which might slightly reduce permeability.

The methanone linkage in the molecule acts as a polar functional group, which can influence the overall polarity of the molecule. This linkage can also participate in hydrogen bonding, which might affect the molecule's interaction with the membrane.

Overall, the given molecule exhibits a balance of hydrophobic and hydrophilic properties, with several aromatic and methoxy groups contributing to its lipophilicity. The presence of the piperazine ring and methanone linkage introduces some polarity, but the overall structure suggests that the molecule would have high permeability in the PAMPA assay due to its favorable balance of lipophilicity and structural flexibility.

Final answer: High permeability

------
# 293

**SMILES:** COC1=CC=CC(=C1)NC2=NC(=NC3=CC=CC=C32)C4=CC=NC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex aromatic amine with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including a methoxyphenyl group and quinazoline moiety, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight due to the presence of multiple aromatic rings and heterocyclic structures. While size can be a limiting factor for permeability, the aromatic nature of these rings may help in spanning the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The methoxy group on the phenyl ring introduces some polarity, which can enhance solubility in the aqueous phase and potentially improve membrane permeability. However, the overall polarity is balanced by the large aromatic system, which is predominantly hydrophobic.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its interaction with the lipid bilayer, potentially increasing permeability through π-π interactions with the membrane.

7. **Hydration Energy**: The presence of polar groups, such as the nitrogen atoms in the quinazoline and amine groups, may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule's structural features, including its lipophilicity, aromaticity, and balanced polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 294

**SMILES:** CC1=NC=C(C=C1)C2=CC=C(C=C2)CNC3=NC(=NC=C3C)C4=CC=CC=C4C(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a pyrimidine derivative with several distinct structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of a pyrimidine core is significant. Pyrimidines are known for their planar structure, which can facilitate interactions with lipid bilayers, enhancing permeability. The pyrimidine ring also contributes to the molecule's aromaticity, which can further improve lipophilicity and membrane affinity.

The molecule contains multiple aromatic rings, including a methylpyridine and a methylphenyl group. Aromatic rings increase lipophilicity, which generally enhances permeability. However, the presence of these rings also means the molecule can engage in π-π interactions with the lipid bilayer, potentially affecting its permeation dynamics.

The methyl groups attached to the pyrimidine and phenyl rings increase the molecule's hydrophobic character, which is typically associated with higher permeability. These groups can also influence the steric profile of the molecule, potentially affecting its ability to fit into the membrane.

The pyridine moiety contributes to the molecule's basicity, which can impact its solubility and permeability. However, in this case, the pyridine is part of a larger aromatic system, which may mitigate its polar character and enhance overall lipophilicity.

Overall, the given molecule's combination of aromaticity, hydrophobic substituents, and a planar pyrimidine core suggests that it would exhibit high permeability in the PAMPA assay. The balance of hydrophobic and aromatic characteristics likely allows it to effectively interact with the artificial membrane, facilitating its passage through the lipid bilayer.

Final answer: High permeability

------
# 295

**SMILES:** CCOC(=O)C1=CC=C(C=C1)NC(=O)CSC2=NC3=C(C=C2C#N)N4CCC3CC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an ethyl ester derivative of benzoic acid, which is a common structural motif in many pharmaceuticals. Let's analyze its properties to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings and the ethyl ester group contribute to the lipophilic nature of the molecule. These features enhance its ability to interact with the lipid components of the artificial membrane, suggesting a high permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings and the ester group can help to balance this effect by increasing lipophilicity.

3. **Polarity**: The molecule has a low polar surface area due to the aromatic rings and the ester group, which reduces its overall polarity. This characteristic is favorable for permeability as it allows the molecule to traverse the hydrophobic lipid bilayer more easily.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility required for passage.

6. **Aromaticity**: The presence of aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, enhancing permeability.

7. **Hydration Energy**: The ester group and aromatic rings suggest that the molecule has a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is ideal for permeability in the PAMPA assay.

Overall, the given molecule exhibits properties that are conducive to high permeability in the PAMPA assay, with its lipophilicity, rigidity, and balanced polarity playing significant roles in its ability to traverse the artificial membrane.

Final answer: High permeability

------
# 296

**SMILES:** CC(C1=CC=CC=C1)NC2=C(N=C(O2)C3=CC=C(O3)COC4=CC=C(C=C4)OC)C#N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and methoxyphenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with multiple rings and functional groups. While size can be a limiting factor for permeability, the presence of aromatic and heterocyclic rings can help to maintain a balance between size and permeability.

3. **Polarity**: The methoxy group and the furan ring introduce some degree of polarity, but the overall structure is dominated by non-polar aromatic systems. The low polar surface area and the presence of hydrogen bond acceptors (such as the nitrile group) suggest moderate polarity, which can still allow for some permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The furan and aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the nitrile group and aromatic systems suggests that the molecule has a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to overcome the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is essential for good permeability in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 297

**SMILES:** CCC(C(=O)NC1=CC=C(C=C1)F)SC2=NC3=CC=CC=C3C4=NC(=NN42)CCC5=C(NN=C5C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the 4-fluorophenyl group and the triazoloquinazoline core, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic rings and the triazoloquinazoline core may help to maintain a balance, potentially allowing for moderate permeability.

3. **Polarity**: The molecule contains a polar amide group and a polar thioether linkage. However, the overall polar surface area is relatively low due to the dominance of aromatic and hydrophobic groups. This suggests that the molecule may have a low-to-moderate polar surface area, which can contribute to its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The triazoloquinazoline core provides a rigid structure, which can enhance the molecule's ability to permeate the membrane by reducing conformational flexibility.

6. **Aromaticity**: The presence of multiple aromatic rings, including the triazoloquinazoline and the 4-fluorophenyl groups, can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of hydrophobic and aromatic groups suggests that the molecule may have a lower hydration energy, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it may have a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

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# 298

**SMILES:** C1=CC=C2C(=C1)C3=C(C2=O)C(SC4=CC=CC=C4N3)C5=CC=CO5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a furan ring and a spirobenzothiophene moiety contributes to the lipophilic nature of the molecule. These aromatic and heterocyclic components enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high degree of lipophilicity.

2. **Molecular Size and Weight**: The spirocyclic structure and the overall molecular framework suggest a relatively large and rigid structure. While size is a factor in permeability, the spiro configuration may confer some rigidity that aids in permeation by maintaining a consistent orientation and interaction with the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the predominance of aromatic and non-polar heterocycles. This low polarity is beneficial for permeability as it allows the molecule to traverse the hydrophobic environment of the lipid bilayer more effectively.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid membranes due to their interaction with polar head groups of the membrane.

5. **Aromaticity**: The presence of aromatic rings, such as the furan and benzothiophene moieties, can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

6. **Hydration Energy**: The aromatic and heterocyclic nature of the molecule likely results in a lower hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests a favorable membrane affinity, which is crucial for its permeability in the PAMPA assay.

Overall, the given molecule exhibits a combination of lipophilicity, rigidity, low polarity, and favorable membrane interactions, which collectively suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 299

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=C(C=C2)C(=O)NC3=NC(=CS3)C4=CC=CC=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiazole rings, contributes to the lipophilic nature of the molecule. The chloro substituent on the phenyl ring further increases lipophilicity, which generally enhances membrane permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple rings and functional groups. While the aromatic rings and heterocyclic thiazole contribute to a larger molecular size, the overall structure is still compact enough to potentially allow for sufficient permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall balance of lipophilic and polar groups suggests moderate polarity, which is common in many bioactive compounds.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by a charge.

5. **Rigidity**: The aromatic and heterocyclic rings impart a degree of rigidity to the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The presence of multiple aromatic systems can influence the molecule's interaction with the lipid bilayer, potentially enhancing its permeability through hydrophobic interactions.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups suggests that the molecule may have moderate hydration energy, which can influence its permeability.

8. **Membrane Affinity**: The given molecule's structural features suggest a balanced affinity for both aqueous and lipid environments, which is often desirable for good permeability in PAMPA assays.

Overall, considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 300

**SMILES:** CC[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)OC(=O)C)CCC4=C/C(=N/O)/CC[C@H]34

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a steroid, which typically exhibits a balance of hydrophobic and hydrophilic properties that facilitate membrane permeability. Steroids are known for their ability to traverse cellular membranes due to their planar structure and lipophilic nature.

The presence of an ethyl group and an ethylidene moiety contributes to the lipophilicity of the molecule, enhancing its ability to interact with the lipid components of the artificial membrane. The cyclopenta[a]phenanthrene core structure is a hallmark of steroid frameworks, providing rigidity and a planar conformation that can facilitate membrane passage.

The hydroxyimino group introduces a degree of polarity, which may influence the molecule's interaction with the aqueous environment and the lipid bilayer. However, in the context of steroids, this functional group is likely to be less dominant in terms of permeability compared to the overall hydrophobic character.

The acetate ester group can also impact the molecule's solubility and permeability. Esters are generally more lipophilic than their corresponding acids, which can enhance membrane permeability. However, esters can also be hydrolyzed, which might affect the stability of the molecule in the membrane environment.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay, owing to its steroid backbone, lipophilic substituents, and moderate polar functional groups.

Final answer: High permeability

------
# 301

**SMILES:** CC1=C(C=CC2=C1OC(CC2)(C)C)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a derivative of 1-benzopyran, which is a bicyclic structure consisting of a benzene ring fused to a pyran ring. This core structure is significant in determining the molecule's properties.

1. **Lipophilicity**: The presence of methyl groups and the aromatic benzene ring contribute to the lipophilic nature of the molecule. These groups increase the hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The dihydrochromen structure indicates a partially saturated pyran ring, which reduces the overall molecular size compared to a fully aromatic chromen. This reduction in size can enhance permeability by allowing the molecule to fit more easily through the membrane.

3. **Polarity**: The hydroxyl group (–OH) on the benzopyran ring introduces some polarity, which can affect the molecule's solubility and permeability. However, the overall structure is more lipophilic than polar, suggesting that the hydroxyl group may not significantly hinder permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The bicyclic structure provides a certain degree of rigidity, which can facilitate passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The aromatic benzene ring can interact with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the hydroxyl group and the overall structure suggest that the molecule has a moderate hydration energy, which can influence its interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties, along with the structural features, suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the structural features of the given molecule, including its lipophilicity, molecular size, and balanced polarity, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 302

**SMILES:** CCN(CC)S(=O)(=O)C1=CC=CC(=C1)C(=O)NC2=CC=C(C=C2)C#N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a benzamide derivative with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzamide and the phenyl group, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively small, which is beneficial for permeability as smaller molecules can more easily traverse the membrane.

3. **Polarity**: The molecule contains both a cyano group and amide linkages, which introduce polar characteristics. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can favor permeability.

4. **Charge**: The molecule is neutral, which is generally favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings and the amide linkage contribute to a relatively rigid structure, which can enhance membrane permeability by reducing the flexibility and conformational changes required for passage through the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the cyano and amide groups may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is beneficial for permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a moderate size, and a balanced affinity for the membrane, suggesting that it would have high permeability in the PAMPA assay.

Final answer: High permeability

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# 303

**SMILES:** COC(=O)CNC(=O)C1=NC(=C2N1C=CN=C2)C3=C(C=C(C=C3)Cl)Cl

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the dichlorophenyl group contributes to the lipophilic nature of the molecule. Chlorine atoms increase the lipophilicity due to their electron-withdrawing properties, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a methyl ester group and an imidazo[1,2-a]pyrazine ring, which contribute to its overall polarity. However, the dichlorophenyl group and the aromatic imidazo[1,2-a]pyrazine ring system also provide significant hydrophobic character, balancing the polarity. The balance between hydrophilic and hydrophobic regions is crucial for membrane permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The imidazo[1,2-a]pyrazine ring system introduces rigidity to the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings present in the molecule can facilitate interactions with the lipid bilayer through π-π interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the ester and imidazo[1,2-a]pyrazine, may lead to moderate hydration energy, which can influence the molecule's solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and rigidity, along with the presence of aromatic systems, suggests that while the molecule can interact with the lipid bilayer, its size and complexity may limit its overall permeability.

Final answer: Low-to-moderate permeability

------
# 304

**SMILES:** CC(C)(C)OC(=O)N1CCN(CC1)C2=CC=C(C=C2)NCC3=CC=C(O3)C4=CC=C(C=C4)C#N

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and furanyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of multiple aromatic rings and a bulky tert-butyl ester group may limit its permeability due to steric hindrance.

3. **Polarity**: The molecule contains a cyano group and a piperazine ring, which introduce polar characteristics. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can interact with both the aqueous and lipid phases of the membrane.

5. **Rigidity**: The aromatic rings and the furan moiety contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the cyano and ester functionalities may reduce the hydration energy, aiding in membrane permeation.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions suggests that the molecule has a moderate affinity for the membrane, which is beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilic and polar characteristics, along with the structural rigidity and aromaticity, supports its ability to traverse the artificial membrane, but the large size and bulky tert-butyl ester group may limit its permeability compared to smaller or less complex molecules.

Final answer: Low-to-moderate permeability

------
# 305

**SMILES:** CC1=CC=C(C=C1)N(C)S(=O)(=O)C2=CC=C(C=C2)C3=CN=C(O3)C4CC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of a cyclopropyl group and a methylaniline moiety contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a potential for high permeability.

2. **Molecular Size and Weight**: The molecule is relatively large due to the presence of multiple aromatic rings and heterocyclic components. While size can be a limiting factor for permeability, the balance of lipophilicity and rigidity might still allow for moderate permeability.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall structure, with its aromatic and cyclopropyl groups, suggests a balance that might favor permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The oxazole ring and aromatic systems contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility required for passage.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide, may lead to moderate hydration energy, which can influence the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components suggests that the molecule has a balanced affinity for both phases, which is generally favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 306

**SMILES:** CC1=CC(=C(C=C1)C)CN2CCC(CC2)CNC(=O)NC3=C(C=C(C=C3)Br)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The presence of bromo and methyl groups on the phenyl rings increases the lipophilicity of the molecule. This suggests that the molecule may have a higher permeability due to its ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.5 g/mol. While size is a factor in permeability, the presence of aromatic rings and flexible linkages may allow it to fit within the membrane despite its size.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of a relatively non-polar character. This low polarity suggests that the molecule can traverse the hydrophobic environment of the artificial membrane more easily.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings contributes to a degree of rigidity, which can enhance the ability of the molecule to permeate the membrane by maintaining a stable conformation.

6. **Aromaticity**: The aromatic rings in the structure can interact with the lipid bilayer, potentially enhancing lipophilic interactions and aiding in permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less likely to be strongly bound to water, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable membrane affinity, which is beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and favorable structural characteristics for membrane interaction.

Final answer: High permeability

------
# 307

**SMILES:** CCOC(=O)C1=CC(=NC2=C1C(=NN2CCC#N)C)C3=CC=CO3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a furan ring and a pyrazolo[1,5-a]pyrimidine core contributes to the lipophilic nature of the molecule. These heterocyclic rings are known to enhance lipophilicity, which generally increases permeability up to a certain threshold.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a limiting factor for permeability, the presence of multiple rings and functional groups may allow for some degree of flexibility and conformational adaptability, which can mitigate this effect.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar aromatic and heterocyclic rings. However, the ethyl ester group and the furan ring introduce some degree of polarity. The balance between these polar and non-polar regions can influence the overall permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged species typically have reduced diffusion through lipid membranes.

5. **Rigidity**: The pyrazolo[1,5-a]pyrimidine core and the furan ring contribute to the rigidity of the molecule. While rigidity can enhance permeability by allowing the molecule to maintain a favorable conformation for interaction with the membrane, it can also hinder permeability if the rigidity restricts conformational flexibility.

6. **Aromaticity**: The aromatic nature of the furan and pyrazolo[1,5-a]pyrimidine rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups, such as the ester and furan, may reduce the hydration energy of the molecule, which can enhance its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable conformational properties.

Final answer: High permeability

------
# 308

**SMILES:** CNC1=NC2=C(S1)C(CC(=O)N2)C3=CC=CC=C3F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a fluorophenyl group contributes to the lipophilic nature of the molecule. Fluorine atoms can enhance lipophilicity due to their electronegativity, which can increase the molecule's ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the specific arrangement of the thieno[2,3-d]pyrimidin core may allow for some flexibility and conformational adaptability, which can aid in permeation.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of a methylamino group and the absence of multiple polar functional groups. This suggests that the molecule is relatively non-polar, which is favorable for permeability through the lipid-rich artificial membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid bilayers.

5. **Rigidity**: The thieno[2,3-d]pyrimidin core provides a degree of rigidity, which can enhance the molecule's ability to permeate the membrane by maintaining a consistent conformation that can interact effectively with the lipid bilayer.

6. **Aromaticity**: The aromatic fluorophenyl group can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the given molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

------
# 309

**SMILES:** C1CCN(CC1)C2=NC(=CS2)C3=CC=C(C=C3)Br

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a thiazole derivative with a piperidine ring and a bromophenyl group. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of the bromophenyl group contributes to the lipophilic character of the molecule. Bromine is a relatively large halogen, and its presence can enhance lipophilicity due to its electron-withdrawing nature, which can increase the molecule's ability to interact with lipid membranes.

2. **Molecular Size and Weight**: The thiazole ring and the piperidine moiety contribute to the overall molecular size. While the thiazole ring is relatively small, the piperidine ring can increase the molecular weight. However, the overall size is still moderate, which may not significantly hinder permeability.

3. **Polarity**: The thiazole ring contains nitrogen and sulfur, which can introduce some polarity. However, the piperidine ring is non-polar, and the bromophenyl group is also non-polar. The overall polar surface area is relatively low, suggesting moderate to high lipophilicity.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The thiazole ring provides some rigidity, which can help the molecule maintain a stable conformation when interacting with the membrane. This rigidity can enhance permeability by allowing better interaction with the lipid bilayer.

6. **Aromaticity**: The bromophenyl group introduces aromaticity, which can enhance lipophilicity and facilitate interactions with the lipid bilayer through π-π interactions.

7. **Hydration Energy**: The presence of the thiazole and piperidine rings suggests that the molecule may have moderate hydration energy, which can influence its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule's structural features suggest it would have high permeability in the PAMPA assay due to its lipophilicity, moderate size, and balanced polarity.

Final answer: High permeability

------
# 310

**SMILES:** C1CC2=C(C(N=C(N2)NC3=NC4=C(O3)C=CC=C4Cl)C5=C(C=NN5)Cl)C(=O)C1

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, including the chloro-substituted benzoxazole and the pyrimidine rings, suggests a significant degree of lipophilicity. This lipophilicity is likely to enhance the molecule's ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a limiting factor for permeability, the presence of multiple rings and heteroatoms may create a rigid structure that could facilitate passage through the membrane.

3. **Polarity**: The molecule contains several nitrogen and oxygen atoms, contributing to its polar surface area. However, the overall polarity is balanced by the extensive aromatic system, which may reduce the molecule's solubility in water and enhance its interaction with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The presence of multiple aromatic and heterocyclic rings suggests a high degree of rigidity, which can improve the molecule's ability to permeate the membrane by reducing its flexibility and conformational changes.

6. **Aromaticity**: The aromatic rings, particularly the benzoxazole and pyrimidine, contribute to the molecule's lipophilicity and may facilitate interactions with the lipid bilayer through π-π stacking or hydrophobic interactions.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 311

**SMILES:** COC1=C(C=C(C=C1)S(=O)(=O)N2CCOCC2)NC(=O)C3=CC(=CC=C3)N4C=CC=C4

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of methoxy and sulfonyl groups, along with aromatic rings, suggests that the given molecule has a moderate to high lipophilicity. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule contains multiple aromatic rings and a sulfonyl group, which contribute to its overall size and molecular weight. While larger molecules can have lower permeability due to size constraints, the presence of these groups may also facilitate interactions with the membrane, potentially offsetting the size effect.

3. **Polarity**: The molecule has a polar sulfonyl group and a pyrrole ring, which can contribute to its overall polarity. However, the methoxy group and aromatic rings also provide hydrophobic character, resulting in a balanced polarity that may favor membrane permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and sulfonyl group contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of multiple aromatic rings can increase lipophilicity and facilitate interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it may have a moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The combination of hydrophobic and hydrophilic groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 312

**SMILES:** CC1=CC2=C(C=C1)SC3=C(C=C(C=C3)C(=O)NC4CCCC4)N=C2C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a dibenzothiazepine, which is a tricyclic compound consisting of two benzene rings fused to a thiazepine ring. This structure contributes to its aromaticity and rigidity, which can enhance its lipophilicity and ability to permeate lipid membranes.

The presence of methyl groups on the benzene rings increases the lipophilicity of the molecule, potentially improving its permeability through the hydrophobic environment of the artificial membrane. The carboxamide group introduces some polarity, but its relatively small size and the presence of the aromatic system may allow it to interact favorably with the lipid bilayer, enhancing permeability.

The cyclopentyl group attached to the nitrogen atom in the carboxamide moiety adds to the hydrophobic character of the molecule, which can further increase its permeability. However, the overall balance of hydrophobic and hydrophilic properties, along with the molecular size and rigidity, will determine the final permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its aromaticity, lipophilicity, and moderate polarity.

Final answer: High permeability

------
# 313

**SMILES:** C1CN(CCN1)C2=NC(=CS2)C3=CC=C(C=C3)Br

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a bromophenyl group contributes to the lipophilic character of the molecule. Bromine is a relatively large halogen, and its presence can enhance the lipophilicity of the molecule, which generally increases permeability up to a certain threshold.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large, with a significant number of atoms. This size can potentially limit permeability due to steric hindrance and difficulty in navigating the lipid bilayer. However, the specific arrangement of functional groups and rings can mitigate this effect.

3. **Polarity**: The molecule contains a piperazine ring, which is a nitrogen-containing heterocycle. Piperazine is relatively polar, which can enhance solubility in aqueous environments but may also limit permeability through the lipid bilayer. The balance between lipophilicity and polarity is crucial in determining permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The thiazole ring contributes to the rigidity of the molecule. Rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the lipid bilayer.

6. **Aromaticity**: The bromophenyl group introduces aromaticity, which can influence lipophilicity and interactions with the lipid bilayer. Aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the nitrogen atoms in the piperazine and thiazole rings, can lead to moderate hydration energy. This can affect the molecule's ability to permeate the membrane, as higher hydration energy typically reduces permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and rigidity, along with the presence of aromatic and heterocyclic components, suggests that while it may have some difficulty navigating the lipid bilayer, it should still exhibit reasonable permeability.

Final answer: Low-to-moderate permeability

------
# 314

**SMILES:** COC1=CC=CC=C1N2C=NC3=C2C=CC(=C3)C(=O)N4CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzimidazole and methoxyphenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a critical factor in permeability, the presence of multiple aromatic rings and a flexible linker may allow the molecule to adopt a conformation that minimizes steric hindrance and facilitates passage through the membrane.

3. **Polarity**: The methoxy group on the phenyl ring introduces some polarity, which can enhance solubility in the aqueous phase and potentially improve membrane permeability by facilitating interactions with the polar head groups of the artificial membrane.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid bilayers due to their inability to interact favorably with the hydrophobic lipid tails.

5. **Rigidity**: The benzimidazole core provides a degree of rigidity to the molecule, which can help in maintaining a favorable orientation for interaction with the membrane. This rigidity can also reduce the likelihood of the molecule adopting a conformation that would hinder its permeability.

6. **Aromaticity**: The aromatic systems in the molecule contribute to its overall lipophilicity and may also participate in π-π interactions with the aromatic residues of the artificial membrane, further enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the methoxy group, may lower the hydration energy of the molecule, facilitating its transition through the aqueous environment surrounding the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is typically desirable for good permeability in PAMPA assays.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, size, polarity, and rigidity, as well as its neutral charge and aromatic character.

Final answer: High permeability

------
# 315

**SMILES:** C1=CC2=C(C=CC(=C2N=C1)O)CNC3=C(C=C(C=C3)F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a hydroxyquinoline derivative, which is known for its potential biological activity and ability to interact with biological membranes. Let's analyze its properties to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the quinoline moiety, which includes aromatic rings, contributes to the lipophilicity of the molecule. This aromatic system can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively small, which is beneficial for permeability. Smaller molecules generally have higher permeability as they can more easily pass through the membrane.

3. **Polarity**: The hydroxyquinoline structure introduces some polarity due to the hydroxyl group. However, the overall polarity is balanced by the lipophilic aromatic rings, which may allow the molecule to maintain a moderate level of permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability. Charged molecules often have reduced permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The quinoline core provides a rigid structure, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings in the quinoline and difluorophenyl groups contribute to the molecule's lipophilicity and may enhance its ability to interact with the lipid bilayer, potentially increasing permeability.

7. **Hydration Energy**: The presence of the hydroxyl group and the overall structure of the molecule may result in moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the membrane.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic properties in the given molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, size, and structural rigidity, as well as its neutral charge and moderate polarity.

Final answer: High permeability

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# 316

**SMILES:** CC(=O)NC1=CC=C(C=C1)OCC2=C(C=CC(=C2)C3=NC4=CC=CC=C4C(=O)N3CC5=CC=CC=C5)OC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a member of quinazolines, which are known for their diverse biological activities. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and quinazoline rings, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple aromatic rings and a quinazoline core. While the size of the molecule is moderate, the presence of these rings may still allow for sufficient permeability, but it might be limited by steric hindrance.

3. **Polarity**: The molecule contains several polar functional groups, including methoxy and acetamide groups. However, the overall polar surface area is relatively low due to the dominance of aromatic rings, which may contribute to a balance between hydrophilic and lipophilic properties. This balance can favor moderate permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The quinazoline core and aromatic rings impart a degree of rigidity to the molecule. This rigidity can enhance the ability of the molecule to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic rings in the structure can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can influence its interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic properties, along with the structural features, suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, structural rigidity, and favorable interactions with the lipid bilayer.

Final answer: Moderate permeability.

------
# 317

**SMILES:** CC(C)OC1=CC=CC(=C1)C2=CSC(=N2)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring indicates a heterocyclic aromatic component, which can contribute to the molecule's lipophilicity and ability to interact with the lipid bilayer. The thiazole ring is known for its electron-rich nature, which can enhance interactions with the membrane.

The phenyl group substituted with an isopropoxy group (propan-2-yloxy) adds to the lipophilic character of the molecule. This group can increase the overall hydrophobicity, potentially improving permeability by enhancing the molecule's ability to dissolve in the lipid bilayer.

The piperidine ring, being a saturated nitrogen-containing heterocycle, can contribute to the molecule's basicity and ability to form hydrogen bonds. This can affect the molecule's solubility and permeability, potentially allowing it to interact with both the aqueous and lipid phases of the membrane.

Overall, the given molecule's combination of aromatic and heterocyclic components, along with its lipophilic substituents, suggests that it may have a balanced affinity for both the aqueous and lipid phases. This balance can result in moderate to high permeability through the artificial membrane, depending on the specific interactions and balance of hydrophilic and hydrophobic properties.

Final answer: Moderate permeability.

------
# 318

**SMILES:** CN1CCN(CC1)C2=CC=C(C=C2)NC3=NC=C(C(=N3)OC4=CC=CC(=C4)NC(=O)C=C)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex aromatic amide with several functional groups that influence its permeability in the PAMPA assay. Let's analyze these properties:

1. **Lipophilicity**: The presence of aromatic rings, such as the pyrimidine and phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings can help to stabilize interactions with the membrane, potentially offsetting this effect.

3. **Polarity**: The molecule contains several polar groups, including the amide linkage and the piperazine ring. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but could also hinder permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily diffuse through the hydrophobic lipid bilayer without being repelled by charge.

5. **Rigidity**: The aromatic rings and the overall structure of the molecule contribute to its rigidity, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can affect its permeability. Lower hydration energy generally improves membrane permeation, but the balance with lipophilic and polar groups will dictate the overall effect.

8. **Membrane Affinity**: The molecule's structure suggests a balanced affinity for both the aqueous and lipid phases, which is typically favorable for permeability in PAMPA assays.

Considering these properties, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic aromatic structure, balanced polarity, and neutral charge.

Final answer: High permeability

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# 319

**SMILES:** CCCOC(=O)C1=CC=C(C=C1)OC2=C(NN=C2C3=C(C=C(C=C3)O)O)C

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a benzoate ester, which suggests that it has an ester functional group linked to a benzoic acid moiety. This structural feature can influence its permeability by affecting its lipophilicity and solubility.

The presence of hydroxyl groups on the phenyl and pyrazole rings increases the molecule's polarity, which can enhance its solubility in aqueous environments. However, these hydroxyl groups also contribute to hydrogen bonding, which can affect the molecule's interaction with the lipid bilayer of the artificial membrane.

The pyrazole ring is a heterocyclic aromatic compound, which can contribute to the molecule's overall aromaticity. Aromaticity can enhance lipophilicity, potentially improving membrane permeability. However, the balance between the aromatic and polar components will determine the overall permeability.

The ester linkage in the benzoate moiety can also influence the molecule's permeability. Esters are generally more lipophilic than their corresponding acids, which can enhance membrane permeability. However, the ester group may also be susceptible to hydrolysis, which could affect the molecule's stability and permeability.

Overall, the given molecule's structure suggests a balance between lipophilic and polar characteristics, which may result in moderate permeability through the artificial membrane. The presence of aromatic rings and hydroxyl groups indicates potential for both hydrophobic interactions and hydrogen bonding, which can further influence its permeability profile.

Final answer: Low-to-moderate permeability

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# 320

**SMILES:** C1CN(CCC1C(=O)N)C2=NC(=CS2)C3=CC=CC=C3F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring, which is a heterocyclic compound containing both sulfur and nitrogen, contributes to the molecule's aromaticity and potential for electronic interactions. The thiazole ring can enhance the molecule's lipophilicity, which is generally associated with increased permeability.

The fluorophenyl group introduces a fluorine atom, which can increase the lipophilicity of the molecule due to its electronegativity and ability to form strong dipole interactions. This can further enhance the molecule's ability to permeate the lipid bilayer.

The piperidine ring is a saturated six-membered ring that provides a degree of rigidity and can influence the molecule's overall conformation. This rigidity can help the molecule maintain a favorable orientation for permeation through the membrane.

Overall, the given molecule's combination of aromaticity, lipophilicity, and structural rigidity suggests that it would have high permeability in the PAMPA assay. The presence of the fluorophenyl group and thiazole ring likely contribute to its ability to interact favorably with the lipid components of the artificial membrane, enhancing its permeability.

Final answer: High permeability

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# 321

**SMILES:** C1C(C2(CN1CC3=CC=C(C=C3)O)CN(C2)C4=CC=CC=C4)CNC5=CC=CC=C5

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of phenyl groups and the overall aromatic nature of the molecule contribute to its lipophilicity. Aromatic rings are known to enhance lipophilicity, which generally increases permeability up to a certain threshold. However, the balance with other polar groups will determine the overall permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large and complex structure, which may limit its permeability due to steric hindrance. Larger molecules often have lower permeability because they may not fit easily through the artificial membrane.

3. **Polarity**: The molecule contains hydroxyl groups, which contribute to its polarity. The presence of these groups can increase the polar surface area, potentially reducing permeability. However, the balance between hydrophilic and hydrophobic regions is crucial, and the overall effect will depend on the specific arrangement and number of these groups.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged species typically have lower permeability due to their interaction with the aqueous environment and difficulty in crossing lipid bilayers.

5. **Rigidity**: The bicyclic structure of the molecule contributes to its rigidity. Rigidity can enhance permeability as it allows the molecule to maintain a specific conformation that can interact favorably with the membrane.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and influence interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of hydroxyl groups suggests that the molecule may have moderate hydration energy, which can affect its solubility and permeability. Lower hydration energy generally improves membrane permeation.

8. **Membrane Affinity**: The balance of hydrophilic and hydrophobic regions in the molecule suggests that it may have a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and structural rigidity suggests that it can interact favorably with the artificial membrane, but the large and complex structure may limit its permeability to some extent.

Final answer: Low-to-moderate permeability

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# 322

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=C(C=C2)F)C(=O)NC3=NC(=CS3)C4=CC=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of a fluorophenyl group and a thiazole ring suggests that the molecule is relatively lipophilic. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and size due to the presence of multiple aromatic rings and a sulfonamide group. While larger molecules can have lower permeability, the specific arrangement of these groups may still allow for sufficient permeation.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall structure, with its aromatic rings, suggests that the molecule is more lipophilic than polar.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The aromatic rings and thiazole ring contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility required for passage.

6. **Aromaticity**: The presence of aromatic rings can increase lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The sulfonamide group and aromatic rings may lower the hydration energy of the molecule, making it easier for the molecule to permeate the membrane by reducing the energy required to escape the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which can enhance its permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 323

**SMILES:** C1=CSC(=C1)C2=NN=C(O2)NC(=O)C3=CC=C(C=C3)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of a chlorobenzamide moiety indicates that the molecule has a degree of lipophilicity due to the chloro substituent on the benzene ring. This can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

Secondly, the oxadiazole ring contributes to the molecule's overall electronic properties and rigidity. The oxadiazole is a heterocyclic aromatic compound, which can enhance the molecule's lipophilicity and ability to penetrate lipid membranes. The aromatic nature of the oxadiazole may also facilitate π-π interactions with the lipid bilayer, further aiding in permeability.

The thiophene ring, another aromatic heterocycle, adds to the molecule's lipophilic character. Thiophene is known for its ability to enhance membrane permeability due to its planar structure and electron-rich nature, which can interact favorably with the lipid bilayer.

The amide linkage in the benzamide group is relatively polar, but the overall structure of the given molecule is dominated by its aromatic and lipophilic components, which likely outweigh the polar characteristics. This suggests that the molecule's polar surface area and hydrogen bonding capacity are not significant enough to hinder its permeability.

Overall, the given molecule's combination of aromatic rings, lipophilic substituents, and heterocyclic components suggests that it would exhibit high permeability in the PAMPA assay. The balance of lipophilicity, rigidity, and aromaticity likely facilitates its diffusion through the artificial membrane.

Final answer: High permeability

------
# 324

**SMILES:** CN1CCCN(CC1)C(C2=CC=CC=C2)C3=CC=C(C=C3)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a diarylmethane, which typically consists of a methane backbone substituted with two aryl groups. This structural feature can influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of two aromatic rings, one of which is a chlorophenyl group, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid-rich artificial membrane, as lipophilic compounds tend to dissolve better in lipid environments.

2. **Molecular Size and Weight**: The given molecule has a relatively moderate molecular size and weight due to the presence of the piperazine ring and the diarylmethane structure. While larger molecules can have issues with permeability, the balance of the aromatic groups and the piperazine ring may still allow for sufficient diffusion through the membrane.

3. **Polarity**: The piperazine ring introduces some degree of polarity to the molecule, which can affect its solubility and permeability. However, the overall structure, dominated by the lipophilic aromatic rings, suggests that the molecule's polarity is not a significant barrier to permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the membrane, potentially aiding in the permeation process.

7. **Hydration Energy**: The presence of the piperazine ring and the aromatic groups may lower the hydration energy of the molecule, facilitating its passage through the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the given molecule suggests it has a favorable membrane affinity, which can enhance its permeability.

Overall, the structural features of the given molecule, such as its lipophilicity, aromaticity, and rigidity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 325

**SMILES:** CN(CC1=CC=C(C=C1)/C=C/C(=O)NO)CC23CC4CC(C2)CC(C4)C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of aromatic rings and other structural features may still allow it to permeate the membrane, but it might not be as permeable as smaller molecules.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and the absence of highly polar functional groups. This low polarity can enhance its permeability through the hydrophobic membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings and the overall structure of the molecule contribute to a certain degree of rigidity. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and balanced structural features that facilitate interaction with the artificial membrane.

Final answer: High permeability

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# 326

**SMILES:** CC(C)(C#N)C1=CC=C(C=C1)N2C3=C4C=C(C=CC4=NC=C3COC2=O)C5=CC6=CC=CC=C6N=C5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the quinoline and nitrilephenyl groups, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, as indicated by its molecular formula. Large molecules often have lower permeability due to steric hindrance and difficulty in navigating the lipid bilayer. However, the specific arrangement of functional groups and rings might still allow for sufficient permeability.

3. **Polarity**: The molecule contains a nitrile group, which can contribute to polarity. However, the overall structure is dominated by aromatic and hydrophobic components, suggesting that the polar surface area is not high enough to significantly impede permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a fused heterocyclic system like quinoline contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by maintaining a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability. However, this effect is balanced by the overall size of the molecule.

7. **Hydration Energy**: The presence of nitrile and aromatic groups suggests that the hydration energy of the molecule is relatively low, which can facilitate membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 327

**SMILES:** CN1CCN(CC1)C2=NC3=C(C=CC(=C3)Cl)NC4=CC=CC=C42

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a dibenzodiazepine, which is a class of compounds known for their psychoactive properties. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the dibenzodiazepine core, contributes to the lipophilic nature of the molecule. This lipophilicity is generally associated with increased permeability, as it facilitates passage through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The dibenzodiazepine structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the specific arrangement of the rings and substituents can influence the overall size and shape, potentially allowing for sufficient permeation.

3. **Polarity**: The molecule contains a chloro substituent, which can increase its polarity. However, the overall polarity is balanced by the aromatic rings and the non-polar piperazine moiety, which may not significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the diazepine core provide a degree of rigidity, which can enhance the molecule's ability to permeate the membrane by maintaining a consistent shape that can interact effectively with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the dibenzodiazepine core can enhance lipophilicity and facilitate interactions with the lipid bilayer, contributing to permeability.

7. **Hydration Energy**: The presence of the piperazine ring and the chloro substituent may lower the hydration energy, making the molecule less water-soluble and thus more likely to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable molecular interactions with the artificial membrane.

Final answer: High permeability

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# 328

**SMILES:** CCC1=CC=C(C=C1)NC(=O)C2=NN3C=CC=NC3=C2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a certain degree of lipophilicity due to the presence of an aromatic ring. Aromatic rings generally enhance lipophilicity, which can improve permeability through lipid membranes. 

The presence of the pyrazolo[1,5-a]pyrimidine core indicates a heterocyclic structure that can contribute to the molecule's rigidity and planarity. This rigidity can facilitate passage through the membrane by reducing the molecule's flexibility and allowing it to fit more easily into the lipid bilayer.

The ethylphenyl group attached to the nitrogen atom of the carboxamide moiety adds to the lipophilic character of the molecule. This group can enhance the molecule's ability to interact with the hydrophobic environment of the artificial membrane.

The carboxamide functional group is polar, but in this context, it is likely balanced by the overall lipophilicity of the molecule. The presence of this group can also contribute to hydrogen bonding, which may aid in the molecule's interaction with the membrane.

Overall, the given molecule's structure suggests that it has a balanced lipophilicity and rigidity, which are conducive to high permeability in the PAMPA assay. The aromatic and heterocyclic components enhance its ability to interact with the lipid membrane, while the carboxamide group provides a degree of polarity that may facilitate its passage through the membrane. Therefore, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 329

**SMILES:** CC1=NN2CCCN(C2=C1C3=CC=CC=C3C4=CC=CC=C4)CC5CC5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl and cyclopropylphenyl groups, contributes to the lipophilic nature of the molecule. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The overall size of the molecule is relatively large due to the presence of multiple aromatic rings and a pyrazolo[1,5-a]pyrimidine core. While size can be a limiting factor for permeability, the specific arrangement and rigidity of the rings might allow for sufficient permeation.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the absence of multiple polar functional groups. This characteristic is favorable for permeability, as it allows the molecule to interact more effectively with the hydrophobic environment of the artificial membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The presence of a cyclopropyl group and the fused ring system contributes to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to permeate the membrane by reducing its flexibility and conformational changes, which might otherwise hinder passage.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also may facilitate interactions with the lipid bilayer through π-π stacking or van der Waals interactions, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy suggests that the molecule is less likely to form strong interactions with water, which can aid in its permeation through the membrane by reducing the energy required for transition.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the molecule suggests a moderate affinity for both the aqueous and lipid phases, which is often desirable for good permeability in PAMPA assays.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, rigidity, and balanced polarity.

Final answer: High permeability

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# 330

**SMILES:** CC(C)(C)C1=CC=C(C=C1)N2C=NC3=C2C=CC(=C3)C(=O)N4CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a member of the benzimidazole class, which is known for its biological activity and potential pharmaceutical applications. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of a tert-butyl group attached to a phenyl ring increases the lipophilicity of the molecule. This group is bulky and hydrophobic, which can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The benzimidazole core is relatively small, and the overall molecular size is moderate. This size allows the molecule to fit within the membrane pores, which is beneficial for permeability. However, the presence of the piperidine moiety adds some bulk, which might slightly reduce permeability compared to smaller molecules.

3. **Polarity**: The benzimidazole ring system is relatively polar, and the presence of nitrogen atoms can form hydrogen bonds. However, the overall polar surface area is balanced by the hydrophobic tert-butyl group, suggesting moderate polarity. This balance can favor permeability as it allows the molecule to interact with both the aqueous and lipid phases.

4. **Charge**: The given molecule is neutral, which is generally favorable for permeability as it can diffuse more easily through the lipid bilayer without being repelled by a charge.

5. **Rigidity**: The benzimidazole and phenyl rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The phenyl and benzimidazole rings contribute to the aromatic character of the molecule. Aromaticity can influence lipophilicity and membrane interactions, potentially enhancing permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it may have moderate hydration energy, which can influence its ability to permeate the membrane.

8. **Membrane Affinity**: The combination of hydrophobic and polar features suggests that the given molecule has a balanced affinity for both the aqueous and lipid phases, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, neutral charge, and favorable structural rigidity and aromaticity.

Final answer: High permeability

------
# 331

**SMILES:** C1CN(CCC1C(=O)N)C2=NC(=CS2)C3=CC4=CC=CC=C4C=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key functional groups and structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of a naphthalene moiety, which is a polycyclic aromatic hydrocarbon, contributes significantly to the lipophilicity of the molecule. This aromatic system increases the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a piperidine ring and a thiazole ring, which may limit its permeability due to steric hindrance. However, the balance of these rings with the naphthalene moiety suggests that the molecule might still have sufficient permeability.

3. **Polarity**: The piperidine ring introduces some polarity to the molecule, but the overall structure is dominated by the hydrophobic naphthalene and thiazole rings. The presence of a carboxamide group also adds some polarity, but it is not sufficient to significantly hinder permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic naphthalene and thiazole rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation during passage through the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the naphthalene and thiazole rings can facilitate interactions with the lipid bilayer, potentially enhancing permeability through π-π interactions with the lipid membrane.

7. **Hydration Energy**: The presence of hydrophobic and aromatic groups suggests that the molecule has a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and polar regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule's structural features, such as its lipophilicity, aromaticity, and rigidity, suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 332

**SMILES:** CC1=CC=C(C=C1)N2C(=C3C(=NN(C(=O)C3=N2)CCCC(=O)NCC4=CC=CC=C4F)C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methyl groups and aromatic rings, such as the dimethyl and methylphenyl groups, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular structure due to the presence of multiple rings and substituents. While size can be a limiting factor for permeability, the presence of aromatic rings and methyl groups may help to maintain a balance, allowing for sufficient permeability despite the size.

3. **Polarity**: The molecule contains a low number of polar functional groups, such as the amide linkage and the fluorine atom on the phenyl ring. These groups contribute to a relatively low polar surface area, which is favorable for permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The pyrazolo[1,5-a]pyrimidine core provides a rigid structure, which can enhance the molecule's ability to permeate the membrane by reducing the flexibility that might otherwise hinder passage.

6. **Aromaticity**: The aromatic rings present in the structure contribute to the overall lipophilicity and may also facilitate interactions with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of fluorine and the overall structure of the molecule likely results in a lower hydration energy, which can improve membrane permeation by reducing the energy required to escape the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous phase and the lipid bilayer.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, polarity, and rigidity.

Final answer: High permeability

------
# 333

**SMILES:** C1CC(=O)NC2=C1C=CC(=C2)OCCCCN3CCN(CC3)C4=C(C(=CC=C4)Cl)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of dichlorophenyl and aromatic rings in the structure suggests a significant degree of lipophilicity. This is likely to enhance the molecule's ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.3 g/mol. While size can be a limiting factor for permeability, the presence of aromatic and heterocyclic rings may help to maintain a balance between size and permeability.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of a relatively non-polar character. This low polarity, combined with the presence of hydrogen bond acceptors, suggests that the molecule may have moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without being repelled by charges.

5. **Rigidity**: The presence of aromatic rings and a quinolinone core contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The aromatic rings, including the dichlorophenyl group, can interact with the lipid bilayer, potentially enhancing lipophilic interactions and permeability.

7. **Hydration Energy**: The molecule's hydration energy is lower than that of water, which suggests that it can interact favorably with the lipid environment of the membrane, aiding in permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is conducive to higher permeability.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that are likely to enhance its permeability in the PAMPA assay. These structural features suggest that the molecule would have high permeability through the artificial membrane.

Final answer: High permeability

------
# 334

**SMILES:** CC1CCCN(C1)C(=O)C2=CC3=C(C=C2)N(C=N3)C4=CC=CC(=C4)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the benzimidazole and phenyl groups, contributes to the lipophilic nature of the molecule. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a factor in permeability, the presence of aromatic rings and the overall structure may allow for sufficient flexibility to traverse the membrane.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of its overall non-polar character. This low polarity suggests that the molecule can interact favorably with the hydrophobic environment of the artificial membrane, enhancing its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The benzimidazole and phenyl rings contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also may engage in π-π interactions with the aromatic residues of the membrane, potentially aiding in permeation.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it is less tightly bound to water molecules, which can enhance its ability to permeate the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable affinity for the lipid bilayer, which is essential for high permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 335

**SMILES:** CC(C)N(CCCNC(=O)NC1=CC=C(C=C1)C(C)(C)C)C[C@@H]2[C@@H]([C@H]([C@@H](O2)N3C=C(C4=C(N=CN=C43)N)Br)O)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a tert-butyl group and a bromo-substituted pyrrolopyrimidine moiety suggests a significant degree of lipophilicity. These groups contribute to the overall hydrophobic character of the molecule, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 533. This size can limit permeability due to steric hindrance and the potential for the molecule to interact with multiple sites within the membrane. However, the specific arrangement of functional groups and the presence of aromatic rings may facilitate passage through the membrane.

3. **Polarity**: The molecule contains several polar groups, including hydroxyl groups and an amine group. These groups can form hydrogen bonds, which may enhance solubility in aqueous environments and facilitate interactions with the polar head groups of the artificial membrane. However, the overall polar surface area is relatively low, suggesting that the molecule's lipophilic regions dominate its behavior.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with polar head groups of the membrane.

5. **Rigidity**: The presence of aromatic rings and a pyrrolopyrimidine core contributes to the rigidity of the molecule. This rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings in the structure can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability. However, the balance between hydrophobic and hydrophilic interactions will dictate the overall permeability.

7. **Hydration Energy**: The molecule's hydration energy is likely moderate due to the presence of both hydrophobic and hydrophilic regions. This balance can facilitate membrane permeation by allowing the molecule to interact with both the aqueous and lipid phases.

8. **Membrane Affinity**: The given molecule appears to have a balanced affinity for both the aqueous phase and the lipid bilayer, as indicated by its structural features. This balance is crucial for effective permeation in the PAMPA assay.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 336

**SMILES:** C1=CSC(=C1)C2=CC(=NC(=N2)S(=O)(=O)CCC(=O)NC3=CC=C(C=C3)OC(F)(F)F)C(F)(F)F

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of trifluoromethyl groups and a pentafluorosulfanyl group contributes significantly to the lipophilicity of the molecule. These groups are highly electronegative and increase the overall hydrophobic character, which generally enhances permeability up to a certain threshold.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the artificial membrane.

3. **Polarity**: The molecule contains a sulfonyl group and a pyridine ring, which introduce some degree of polarity. However, the overall effect of these polar groups is mitigated by the strong lipophilic character imparted by the trifluoromethyl and pentafluorosulfanyl groups.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The aromatic rings, including the pyridine and phenyl groups, contribute to the rigidity of the molecule. This rigidity can enhance membrane permeability as it allows for more effective interaction with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings can influence lipophilicity and molecular interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy associated with the trifluoromethyl and pentafluorosulfanyl groups suggests that the molecule has a lower affinity for water, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and balanced structural features that facilitate interaction with the artificial membrane.

Final answer: High permeability

------
# 337

**SMILES:** C1CN(CCC1C(=O)N)C2=NC(=CS2)C3=CC=CC=C3C4=CC=CC=C4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex structure that includes several key components influencing its permeability in the PAMPA assay. Let's break down these components and their impact on permeability:

1. **Biphenyl Structure**: The presence of a biphenyl moiety, which consists of two phenyl rings connected by a single bond, contributes to the lipophilicity of the molecule. This biphenyl structure is known for enhancing hydrophobic interactions, which can increase the molecule's ability to permeate lipid membranes. However, the size and rigidity of the biphenyl system can also limit permeability if it causes steric hindrance or rigidity that prevents the molecule from fitting through the membrane.

2. **Thiazole Ring**: The thiazole ring is a heterocyclic compound containing both sulfur and nitrogen. This ring can contribute to the molecule's overall lipophilicity and may also participate in specific interactions with the membrane, such as hydrogen bonding or π-π interactions with aromatic residues in the lipid bilayer. The presence of the thiazole ring can enhance the molecule's ability to permeate the membrane, but its exact effect depends on the balance with other structural features.

3. **Piperidine Ring**: The piperidine ring is a saturated six-membered ring containing nitrogen, which can introduce some degree of polarity to the molecule. This ring can enhance the molecule's solubility in aqueous environments, which is beneficial for permeability. However, the presence of the nitrogen atom can also introduce a basic site, which might lead to protonation under physiological conditions, potentially reducing permeability due to increased hydrophilicity.

4. **Carboxamide Group**: The carboxamide group is a polar functional group that can form hydrogen bonds with the surrounding environment. While this group can enhance solubility and interaction with the membrane, it may also reduce permeability due to its polar nature. The balance between the polar and non-polar regions of the molecule will determine its overall permeability.

5. **Overall Molecular Properties**: The given molecule has a relatively large molecular size and weight, which may limit its permeability due to steric effects. However, the combination of lipophilic and polar regions suggests that the molecule has a balanced affinity for both aqueous and lipid environments, which is favorable for membrane permeation.

In summary, the given molecule's permeability in the PAMPA assay is likely influenced by its biphenyl and thiazole rings, which enhance lipophilicity, while the piperidine and carboxamide groups introduce some polarity. The balance of these features suggests that the molecule may exhibit moderate permeability, with the potential for high permeability depending on the specific interactions with the artificial membrane.

Final answer: Low-to-moderate permeability

------
# 338

**SMILES:** C1=CC=NC(=C1)C(=O)NC2=CC=C(C=C2)[S+](=O)(NC3=NC=CS3)[O-]

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is an aromatic amide, which suggests it has a certain degree of rigidity and aromatic character. This can influence its permeability by enhancing its lipophilicity and ability to interact with the lipid bilayer of the artificial membrane.

The presence of aromatic rings, such as the pyridine and phenyl groups, contributes to the molecule's lipophilicity, which is generally associated with higher permeability. These aromatic systems can also facilitate π-π interactions with the membrane, potentially enhancing permeability.

The molecule also contains a thiazole ring, which is a heterocyclic aromatic compound. This can contribute to the overall aromatic character and may influence the molecule's ability to traverse the membrane by interacting with the lipid bilayer.

The carboxamide group in the molecule is polar, but its presence is balanced by the overall lipophilic nature of the aromatic rings. This balance can lead to moderate polarity, which is beneficial for permeability as it allows the molecule to interact with both the aqueous and lipid phases.

Overall, the given molecule's structure, with its aromatic rings, moderate polarity, and balanced lipophilicity, suggests that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 339

**SMILES:** CC1=CC=C(C=C1)C2=NC(=NC=C2)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a pyrimidine derivative with a piperidine carboxamide moiety. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of the pyrimidine and piperidine rings, along with the 4-methylphenyl group, suggests a moderate to high lipophilicity. This is because aromatic and heterocyclic rings generally increase lipophilicity, which can enhance membrane permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight due to the presence of multiple rings and functional groups. While this can sometimes hinder permeability, the aromatic and heterocyclic nature of the rings may help to maintain a balance that still allows for significant permeability.

3. **Polarity**: The piperidine and carboxamide groups introduce some polarity to the molecule. However, the overall structure is dominated by the lipophilic pyrimidine and phenyl rings, which likely outweigh the polar contributions, resulting in a moderate lipophilicity.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to a rigid structure, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The pyrimidine and phenyl rings contribute to the aromatic character, which can enhance lipophilicity and membrane affinity.

7. **Hydration Energy**: The presence of polar groups like the carboxamide may lead to some hydration, but the overall structure suggests a lower hydration energy, which can improve membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests it has a favorable membrane affinity, which is conducive to permeability.

Considering these properties, the given molecule is likely to exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 340

**SMILES:** CCOC1=CC=CC=C1N2CC(CC2=O)C3=NC4=CC=CC=C4N3CCOC5=CC=C(C=C5)C(C)(C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl and benzimidazole groups, contributes to the lipophilic nature of the molecule. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the presence of flexible ethoxy and phenyl ethyl linkers might help in accommodating the molecule within the membrane.

3. **Polarity**: The molecule has a low polar surface area due to the predominance of aromatic and alkyl groups over polar functional groups. This low polarity can enhance its ability to permeate the membrane, as it interacts favorably with the hydrophobic lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The benzimidazole and phenyl rings contribute to the rigidity of the molecule. While rigidity can sometimes hinder permeability due to limited conformational flexibility, in this case, it may also help the molecule to fit snugly into the membrane, facilitating passage.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the aromatic residues of the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests a moderate affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, moderate size, low polarity, and balanced affinity for the membrane.

Final answer: High permeability

------
# 341

**SMILES:** CCC1=CC=C(C=C1)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@@H]4CC5=CC=CC=C5CN4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of an indole moiety and an aromatic phenyl ring suggests that the given molecule is relatively lipophilic. These aromatic systems contribute to the overall hydrophobic character, which can enhance membrane permeability up to a certain point.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 434. This size can limit permeability due to steric hindrance and the potential for the molecule to interact with multiple sites on the membrane, which may slow down its passage.

3. **Polarity**: The molecule contains several polar groups, including an amide linkage and a secondary amine. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but can also hinder permeability through the lipid bilayer. However, the overall polar surface area is relatively low, suggesting that the molecule's permeability is not severely compromised by polarity.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings and a rigid indole structure suggests that the molecule is relatively rigid. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings contribute to the lipophilicity and may also participate in π-π interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the hydration energy is not excessively high, which can favor membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is generally beneficial for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

------
# 342

**SMILES:** CC1=CC(=C(C=C1)C)CN2C3=C(C=CC(=C3)C(=O)N4CCN(CC4)C5=CC=CC=C5F)S(=O)C6=CC=CC=C6C2=O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the dimethylphenyl and fluorophenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems increase the overall hydrophobic character, which generally enhances permeability up to a certain point.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the artificial membrane.

3. **Polarity**: The molecule contains a piperazine ring, which introduces some degree of polarity. However, the overall structure is dominated by hydrophobic aromatic rings, suggesting that the molecule's polar surface area is not high enough to significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the lipid bilayer.

5. **Rigidity**: The benzo[b][1,4]benzothiazepine core provides a rigid structure, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings contribute to the molecule's lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of fluorine in the fluorophenyl group can lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing its affinity for water.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule's structural features suggest that it would exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 343

**SMILES:** CCOC(=O)C1=C(C(=C(N1)C)CCC(=O)N2CCN(CC2)C3=CC=CC(=C3C)C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methyl groups on the pyrrole and phenyl rings increases the lipophilicity of the molecule. This suggests that the molecule may have a high permeability due to its ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings and the ethyl ester group can help to balance this by increasing lipophilicity.

3. **Polarity**: The molecule contains a piperazine ring, which is polar and can form hydrogen bonds. However, the overall polar surface area is relatively low due to the presence of non-polar methyl groups and aromatic rings, which may contribute to moderate permeability.

4. **Charge**: The piperazine ring is neutral, which is favorable for permeability as it allows the molecule to diffuse through the hydrophobic lipid bilayer without being repelled by a charge.

5. **Rigidity**: The aromatic rings and the pyrrole core provide a degree of rigidity to the molecule, which can enhance its ability to permeate the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The aromatic rings contribute to the lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The ester group and the overall structure suggest that the molecule has a lower hydration energy, which can facilitate its passage through the membrane by reducing the energy required to overcome the aqueous environment.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is likely to result in moderate to high permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable structural features for membrane interaction.

Final answer: High permeability

------
# 344

**SMILES:** CC(=O)NC1=CC=C(C=C1)C(=O)NC2=CC3=C(C=C2)SC4=CC=CC=C4C(=O)N3C5CCCC5

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzothiazole and phenyl groups, contributes to the lipophilic nature of the molecule. This lipophilicity is likely to enhance its permeability through the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant molecular weight. While size is a factor in permeability, the presence of multiple aromatic rings and a bulky structure may limit its permeability due to steric hindrance.

3. **Polarity**: The molecule contains several polar groups, including the acetamide and carbamoyl groups. These groups can form hydrogen bonds, which may reduce its overall lipophilicity and limit its permeability. However, the balance between these polar groups and the lipophilic aromatic rings suggests moderate polarity.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of aromatic rings and a cyclopentane moiety contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation during passage.

6. **Aromaticity**: The aromatic rings can interact with the lipid bilayer through π-π interactions, which may enhance permeability.

7. **Hydration Energy**: The balance of polar and nonpolar regions suggests that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the membrane.

8. **Membrane Affinity**: The molecule's structure suggests a balanced affinity for both aqueous and lipid environments, which is favorable for permeability in the PAMPA assay.

Overall, the given molecule's structural features suggest that it would exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and polar interactions.

Final answer: Low-to-moderate permeability

------
# 345

**SMILES:** CC(=O)C1=CC=CC(=C1)C2=CSC(=N2)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring, which is a heterocyclic compound containing both sulfur and nitrogen, contributes to the molecule's aromaticity and potential for electronic interactions. This can enhance the molecule's lipophilicity, aiding in its permeability through the lipid bilayer.

The phenyl group attached to the thiazole ring further increases the lipophilic character of the molecule, which is generally associated with higher permeability. However, the presence of the acetyl group on the phenyl ring introduces a polar functional group, which can affect the overall polarity of the molecule. This may lead to a balance between hydrophilic and lipophilic properties, potentially enhancing the molecule's ability to interact with both the aqueous and lipid environments.

Overall, the given molecule's structure suggests that it has a balanced lipophilicity and polarity, which could result in moderate to high permeability through the artificial membrane used in the PAMPA assay.

Final answer: Low-to-moderate permeability

------
# 346

**SMILES:** CC(C)C1=CC=CC=C1C2=NC=C(C(=N2)NCC3CCN(C3)C4=NC=CN=C4)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to the properties that influence membrane permeability.

1. **Lipophilicity**: The given molecule contains a fluorophenyl group, which contributes to its lipophilic character. This group can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The presence of a pyrimidine ring and a pyrrolidine moiety suggests a relatively complex structure. While these rings can contribute to specific interactions with the membrane, they may also limit permeability due to their size and potential steric hindrance.

3. **Polarity**: The pyrimidine and pyrrolidine rings introduce some degree of polarity, but the overall structure is balanced by the lipophilic fluorophenyl group. This balance can favor moderate permeability, as the molecule is neither too polar nor too non-polar.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as it can more easily diffuse through the lipid bilayer without encountering electrostatic barriers.

5. **Rigidity**: The aromatic rings, such as the fluorophenyl and pyrimidine, contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation during interaction with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can also influence the molecule's lipophilicity and its ability to engage in π-π interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the nitrogen atoms in the pyrimidine and pyrrolidine rings, may lead to moderate hydration energy. This can affect the molecule's solubility and permeability, with lower hydration energy generally favoring better membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the given molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate to high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, rigidity, and polarity that facilitates interaction with the artificial membrane.

Final answer: Moderate permeability.

------
# 347

**SMILES:** C1CCCN(CC1)C2=NC(=NC3=CC=CC=C32)C4=CC=CC=N4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a pyridine ring and a quinazoline core suggests that the molecule has a degree of lipophilicity. Pyridine is a heteroaromatic ring that can contribute to the molecule's ability to interact with lipid membranes, enhancing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 314.3 g/mol. While size can be a limiting factor for permeability, the presence of multiple aromatic rings and heterocycles may help to maintain a balance between size and permeability.

3. **Polarity**: The molecule contains multiple nitrogen atoms, which can introduce polarity. However, the overall structure, with its aromatic rings, suggests that the polar surface area is not excessively high, which could favor permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The quinazoline and pyridine rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

6. **Aromaticity**: The presence of pyridine and quinazoline rings indicates significant aromatic character, which can enhance lipophilicity and facilitate interactions with the lipid bilayer.

7. **Hydration Energy**: The aromatic and heterocyclic nature of the molecule suggests that it may have a lower hydration energy, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic elements in the molecule suggests that it has a favorable membrane affinity, which is essential for high permeability in the PAMPA assay.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, neutral charge, and favorable aromatic and heterocyclic characteristics.

Final answer: High permeability

------
# 348

**SMILES:** COC1=CC=CC=C1N2CCN(CC2)C3=NC4=C(C=C3)C=C(C=C4)S(=O)(=O)N5CCCCC5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the methoxyphenyl group and the quinoline moiety, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule contains a piperazine ring and a sulfonyl group, which add to its molecular complexity. While these groups can increase the molecular weight, the overall size and weight of the molecule are still relatively moderate, which may not significantly hinder its permeability.

3. **Polarity**: The methoxy group on the phenyl ring and the sulfonyl group introduce some degree of polarity. However, the overall polar surface area is balanced by the lipophilic aromatic systems, which may allow the molecule to maintain a reasonable balance between hydrophilic and lipophilic properties.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The quinoline and piperazine rings contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to fit into the membrane and permeate more efficiently.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the lipid bilayer, potentially enhancing its permeability.

7. **Hydration Energy**: The presence of polar groups like the sulfonyl and methoxy groups may reduce the hydration energy of the molecule, facilitating its passage through the membrane.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic groups suggests that the molecule has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate size, and favorable interactions with the artificial membrane.

Final answer: High permeability

------
# 349

**SMILES:** C1CCC(CC1)C(=O)NCCC2=NC3=CC=CC=C3N2CCOC4=CC=CC=C4N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a member of the benzimidazole class, which is known for its biological activity and potential pharmaceutical applications. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the benzimidazole core, which is aromatic and planar, contributes to the lipophilicity of the molecule. Additionally, the cyclohexanecarboxamide moiety and the 2-aminophenylsulfanyl group also contribute to the overall lipophilic character. This suggests that the molecule may have a moderate to high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings and functional groups, which may increase its molecular weight. However, the presence of the cyclohexane ring and the benzimidazole core suggests that the molecule is not excessively large, which could still allow for reasonable permeability.

3. **Polarity**: The molecule contains several polar functional groups, such as the amide and amino groups. These groups can form hydrogen bonds, which may affect the overall polarity. However, the balance between these polar groups and the lipophilic aromatic rings suggests that the polar surface area is not excessively high, which could favor permeability.

4. **Charge**: The given molecule is neutral, as it does not contain any charged functional groups. This neutrality is favorable for permeability, as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The benzimidazole core provides a rigid structure, which can facilitate passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The aromatic benzimidazole and phenyl rings contribute to the lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the hydration energy might not be excessively high, which could favor membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it may have a favorable affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, molecular size, and structural rigidity, along with a moderate polar surface area and neutral charge.

Final answer: High permeability

------
# 350

**SMILES:** CN1C=CC2=C1C=CC(=C2)C3=CSC(=N3)N4CCC(CC4)C(=O)N

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a piperidinecarboxamide, which is a type of compound that includes a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

Analyzing the properties of the given molecule:

1. **Lipophilicity**: The presence of the indole moiety, which is a bicyclic structure containing an aromatic benzene ring fused to a pyrrole ring, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate lipid membranes.

2. **Molecular Size and Weight**: The overall molecular structure is relatively complex, with multiple rings and functional groups. While the indole and thiazole rings add to the molecular weight, the piperidine and carboxamide groups may contribute to a balance that allows for moderate permeability.

3. **Polarity**: The piperidine ring and the carboxamide group introduce polar characteristics to the molecule. However, the overall polar surface area is balanced by the lipophilic indole and thiazole rings, which may allow for some degree of permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without encountering steric hindrance from charged groups.

5. **Rigidity**: The indole and thiazole rings provide some rigidity to the molecule, which can facilitate its passage through the membrane by maintaining a consistent conformation.

6. **Aromaticity**: The indole and thiazole rings contribute to the aromatic character of the molecule, which can enhance lipophilicity and influence interactions with the lipid bilayer.

7. **Hydration Energy**: The presence of polar groups like the carboxamide may reduce the hydration energy of the molecule, potentially improving its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has an affinity for both the aqueous and lipid phases, which is beneficial for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, as it possesses a balance of lipophilic and polar characteristics, a suitable molecular size, and a neutral charge.

Final answer: Low-to-moderate permeability

------
# 351

**SMILES:** CC(C)CNC1=NC(=NC=C1)NCC2=CSC(=N2)C3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl group and the thiazolopyrimidine moiety, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a moderate molecular size and weight, which is typical for many bioactive compounds. While larger molecules can have reduced permeability due to size constraints, the specific structure of this molecule allows it to navigate through the membrane effectively.

3. **Polarity**: The molecule contains nitrogen atoms in the pyrimidine and thiazole rings, which can contribute to its polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity that may facilitate membrane permeation.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings and heterocyclic structures contribute to a certain degree of rigidity, which can enhance the molecule's ability to permeate the membrane by maintaining a stable conformation during passage.

6. **Aromaticity**: The phenyl and thiazolopyrimidine rings are aromatic, which can further enhance lipophilicity and facilitate interactions with the lipid bilayer, promoting permeability.

7. **Hydration Energy**: The presence of multiple nitrogen atoms and aromatic rings suggests that the molecule has a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophilic and lipophilic components in the molecule suggests that it has a favorable membrane affinity, allowing it to interact effectively with both the aqueous and lipid phases of the membrane.

Overall, the given molecule exhibits a combination of lipophilic, aromatic, and rigid structural features that contribute to its high permeability in the PAMPA assay.

Final answer: High permeability

------
# 352

**SMILES:** COC1=CC=CC(=C1)CNCC2=CC=CN2C3=NN=C(S3)N4CCN(CC4)C5=CC=CC=C5

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several functional groups and aromatic systems, which influence its permeability in the PAMPA assay. Let's break down the structural components and their impact on permeability:

1. **Piperazine Ring**: The presence of a piperazine ring contributes to the molecule's basicity and potential for hydrogen bonding. Piperazine rings are often found in molecules with moderate to high permeability due to their ability to interact with both hydrophilic and hydrophobic environments.

2. **Phenyl Groups**: The molecule contains multiple phenyl groups, which are aromatic and contribute to its lipophilicity. Aromatic rings can enhance membrane permeability by increasing the molecule's ability to interact with the lipid bilayer through π-π interactions and van der Waals forces.

3. **Methoxyphenyl Group**: The methoxy group on the phenyl ring increases the molecule's lipophilicity and can also participate in hydrogen bonding, which may affect its solubility and permeability.

4. **Thiadiazole Ring**: The thiadiazole ring is a heterocyclic component that can contribute to the molecule's overall stability and rigidity. This rigidity can enhance permeability by allowing the molecule to maintain a consistent conformation as it interacts with the membrane.

5. **Piperazine-linked Phenyl Group**: The linkage of a phenyl group to the piperazine ring can further enhance lipophilicity and membrane affinity, promoting permeability.

6. **Overall Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance and the potential for the molecule to be retained in the aqueous phase.

7. **Charge and Polarity**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced diffusion through lipid membranes.

8. **Hydration Energy**: The presence of multiple aromatic and heterocyclic rings suggests that the molecule may have a lower hydration energy, which can improve its ability to permeate the membrane.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromatic content, and balanced polarity. However, its large size and complex structure may limit its permeability to some extent.

Final answer: High permeability

------
# 353

**SMILES:** COC1=CC=CC=C1N2CCN(CC2)CCN(C3=CC=CC=N3)C(=O)C4=CC=C(C=C4)F

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzamide and pyridine moieties, contributes to the lipophilic nature of the molecule. Additionally, the fluorine atom on the phenyl ring can enhance lipophilicity due to its electronegativity, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of flexible linkers, such as the ethyl chain connecting the pyridine and benzamide moieties, may allow some degree of conformational flexibility, which can help the molecule to adapt to the membrane.

3. **Polarity**: The molecule has a moderate polar surface area due to the presence of the pyridine ring and the amide linkage. The pyridine nitrogen can participate in hydrogen bonding, which may affect its interaction with the membrane. However, the overall balance of lipophilic and polar features suggests moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to a degree of rigidity, which can affect the molecule's ability to permeate the membrane. Rigidity can help the molecule maintain a favorable conformation for interaction with the membrane.

6. **Aromaticity**: The aromatic rings can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeation.

7. **Hydration Energy**: The presence of polar groups, such as the amide and pyridine, suggests that the molecule may have moderate hydration energy, which can influence its solubility and permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, molecular size, and polar characteristics suggests that while it may not permeate easily, it should have some degree of membrane penetration.

Final answer: Low-to-moderate permeability

------
# 354

**SMILES:** C1CC1C2=NC3=C(CCN(CC3)CC4=CC=C(C=C4)F)C(=N2)C5=CC=C(C=C5)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and fluorophenyl groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, with multiple rings and functional groups. While size can be a limiting factor for permeability, the presence of a cyclopropyl group and the overall rigidity of the structure may help the molecule maintain a certain degree of conformational flexibility, which can aid in permeation.

3. **Polarity**: The molecule contains a phenolic hydroxyl group, which introduces some degree of polarity. However, the overall effect of this group on permeability is likely mitigated by the extensive hydrophobic regions of the molecule, which dominate its surface characteristics.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The pyridopyrimidine core and the cyclopropyl group contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to fit into and interact with the membrane, potentially improving permeability.

6. **Aromaticity**: The aromatic systems in the molecule can engage in π-π interactions with the lipid bilayer, which may enhance its permeability.

7. **Hydration Energy**: The presence of polar groups, such as the hydroxyl group, suggests that the molecule may have moderate hydration energy. This can influence its solubility and permeability, with lower hydration energy generally favoring better membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typically favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 355

**SMILES:** C1=CC=C(C=C1)C2=CC=C(C=C2)S(=O)(=O)NC3=C(C=CN=C3)C(=O)NC4=NC(=CS4)C5=CC=CC=C5

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The given molecule contains several aromatic rings, including phenyl and pyridine groups, which contribute to its lipophilic nature. This suggests that the molecule may have a high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The presence of multiple aromatic rings and a sulfonamide group indicates a relatively large molecular size. While size can be a limiting factor for permeability, the aromatic nature may help in maintaining a balance, potentially allowing moderate permeability.

3. **Polarity**: The molecule has a sulfonamide group, which introduces some polarity. However, the overall structure is dominated by aromatic rings, which are hydrophobic. This suggests that the molecule may have a low polar surface area, contributing to higher permeability.

4. **Charge**: The given molecule is neutral, as it does not contain any charged functional groups. This neutrality is favorable for permeability, as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings provide a rigid structure, which can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of multiple aromatic systems, including phenyl and pyridine rings, can enhance lipophilicity and influence interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The aromatic and sulfonamide groups suggest that the molecule may have a lower hydration energy, which can enhance its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and balanced structural features.

Final answer: High permeability

------
# 356

**SMILES:** C1=CC=C(C=C1)CNC(=O)C2=NC(=NC=C2Cl)S(=O)(=O)CC3=CC=C(C=C3)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and fluorophenyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and functional groups may allow for specific interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is indicated by the low number of hydrogen bond donors and acceptors. This suggests that the molecule is relatively non-polar, enhancing its ability to permeate the hydrophobic membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced diffusion through lipid membranes.

5. **Rigidity**: The pyrimidine core and aromatic rings contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings, including the phenyl and fluorophenyl groups, can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy suggests that the molecule is less likely to form strong interactions with water, which can aid in its permeation through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for membrane permeability.

Overall, the given molecule exhibits a combination of lipophilicity, rigidity, and a balanced polarity that suggests it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 357

**SMILES:** CCC1=CC(=CC=C1)NS(=O)(=O)C2=CC3=C(C=C2)N(C(C3)C)C(=O)C4CC4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of a cyclopropane ring and a sulfonamide group suggests moderate lipophilicity. Cyclopropane rings are known for their rigidity and can enhance lipophilicity, while the sulfonamide group can contribute to both hydrophilic and lipophilic interactions.

2. **Molecular Size and Weight**: The given molecule has a relatively complex structure with multiple rings, including a dihydroindole moiety and a sulfonamide group. This complexity may limit its permeability due to steric hindrance, but the cyclopropane ring can help reduce the overall molecular size and weight, potentially improving permeability.

3. **Polarity**: The sulfonamide group introduces some polarity, which can enhance solubility in aqueous environments but may also hinder permeability through lipid membranes. However, the overall balance of polar and non-polar groups suggests moderate polarity.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as it can more easily diffuse through the lipid bilayer without encountering charge-related barriers.

5. **Rigidity**: The cyclopropane ring contributes to the rigidity of the molecule, which can enhance its ability to permeate the membrane by reducing flexibility and conformational changes.

6. **Aromaticity**: The presence of an aromatic phenyl group can influence lipophilicity and membrane interactions, potentially enhancing permeability due to favorable hydrophobic interactions with the lipid bilayer.

7. **Hydration Energy**: The balance of hydrophilic and hydrophobic groups in the given molecule suggests that it may have moderate hydration energy, which can influence its permeability by affecting its interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The given molecule's structural features suggest a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between hydrophilic and lipophilic interactions and maintaining a suitable size and rigidity for membrane passage.

Final answer: Low-to-moderate permeability

------
# 358

**SMILES:** CC1=CC(=C(N1C2=CC(=CC=C2)Cl)C)C3=NN=C4N3CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a chlorophenyl group and the trimethylpyrazole moiety contribute to the lipophilic nature of the molecule. These groups increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and rings. While size can be a limiting factor for permeability, the presence of multiple rings and substituents may create a balance that allows for sufficient permeation.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar groups like the chlorophenyl and trimethylpyrazole. This low polarity aids in permeability as it reduces the molecule's affinity for water and enhances its interaction with the lipid membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The triazolopyridine core provides a degree of rigidity to the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings present in the chlorophenyl and pyridine moieties can enhance lipophilicity and may also participate in π-π interactions with the lipid bilayer, potentially aiding in permeation.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, which can enhance its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the molecule suggests it has a favorable membrane affinity, which is crucial for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, neutral charge, and balanced membrane affinity.

Final answer: High permeability

------
# 359

**SMILES:** CC1=CC(=C(N1C2=CC=CC(=C2)C(F)(F)F)C)C3=NN=C4N3CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a trifluoromethyl group attached to a phenyl ring increases the lipophilicity of the molecule. This group is known for enhancing the hydrophobic character, which can improve membrane permeability due to increased solubility in lipid environments.

2. **Molecular Size and Weight**: The molecule contains a tricyclic structure with nitrogen atoms, which contributes to its overall size and weight. While the size of the molecule is relatively large, the presence of multiple rings can also introduce rigidity, which may help in permeating the membrane more efficiently.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the presence of multiple non-polar groups such as methyl groups and the trifluoromethyl group. This low polarity can enhance its ability to permeate the lipid bilayer, as it reduces the energy required for the molecule to transition from an aqueous to a lipid environment.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes due to their interaction with polar head groups of the membrane.

5. **Rigidity**: The tricyclic structure imparts a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing the flexibility required for the molecule to adopt different conformations.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl group, can enhance lipophilicity and facilitate interactions with the lipid bilayer through π-π interactions, potentially improving permeability.

7. **Hydration Energy**: The low hydration energy suggests that the molecule is less tightly bound to water molecules, which can enhance its ability to permeate the membrane by reducing the energy required to release water molecules upon crossing the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for membrane permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its enhanced lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 360

**SMILES:** C1CCN(C1)C2=NC=C(C=C2)CNC(=O)C3=C(C=CC(=C3)Cl)O

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is characterized by several structural features that influence its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

1. **Lipophilicity**: The presence of a chloro group and a hydroxy group on the benzamide moiety suggests moderate lipophilicity. The chloro group can enhance lipophilicity due to its electron-withdrawing nature, while the hydroxy group can contribute to polarity. However, the overall lipophilicity is balanced by the presence of these functional groups.

2. **Molecular Size and Weight**: The molecule is relatively small, which is beneficial for permeability. The benzamide core and the pyridine ring contribute to a compact structure, which can facilitate passage through the membrane.

3. **Polarity**: The hydroxy group and the amide linkage introduce polar characteristics, which can affect the molecule's interaction with the membrane. However, the overall polar surface area is not high enough to significantly impede permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The aromatic rings, including the benzamide and pyridine moieties, contribute to a degree of rigidity. This rigidity can enhance the molecule's ability to interact with the membrane, potentially improving permeability.

6. **Aromaticity**: The aromatic nature of the benzamide and pyridine rings can influence the molecule's lipophilicity and its ability to engage in π-π interactions with the lipid bilayer, which can affect permeability.

7. **Hydration Energy**: The presence of polar groups like the hydroxy and amide groups suggests that the molecule may have moderate hydration energy, which can influence its interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the given molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between hydrophilic and hydrophobic interactions with the artificial membrane.

Final answer: Low-to-moderate permeability

------
# 361

**SMILES:** COC1=CC=C(C=C1)CN2CCN(CC2)C(=O)C3=CC4=C(S3)CCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Piperazine Ring**: The presence of a piperazine ring contributes to the molecule's basicity and potential for hydrogen bonding. Piperazine rings are often found in pharmaceuticals and can enhance solubility and permeability due to their ability to interact with both hydrophilic and hydrophobic environments.

2. **Methoxyphenyl Group**: The methoxy group attached to the phenyl ring increases the lipophilicity of the molecule. This can enhance the molecule's ability to permeate lipid membranes, as lipophilic compounds tend to dissolve more readily in lipid bilayers.

3. **Thieno[2,3-b]pyrrole Moiety**: This bicyclic structure introduces aromaticity and rigidity to the molecule. Aromatic and rigid structures can improve membrane permeability by facilitating interactions with the lipid bilayer and reducing the energy required for passage through the membrane.

4. **Methanone Linkage**: The methanone group acts as a linker between the piperazine and the thieno[2,3-b]pyrrole moiety. This linkage can influence the overall flexibility and conformation of the molecule, potentially affecting its ability to fit into and traverse the membrane.

5. **Overall Molecular Properties**: The combination of these structural features suggests that the given molecule has a balance of hydrophilic and hydrophobic properties, which is conducive to membrane permeability. The piperazine ring provides a degree of solubility and interaction with the aqueous phase, while the methoxyphenyl and thieno[2,3-b]pyrrole groups enhance lipophilicity and membrane affinity.

Based on these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 362

**SMILES:** CC1=CC=C(C=C1)S(=O)(=O)NC2=C(C=CN=C2)C(=O)NC3=NC(=CS3)C4=CC(=CC=C4)OC

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the methoxyphenyl and pyridinyl groups, contributes to the lipophilic nature of the molecule. The methoxy group on the phenyl ring can enhance lipophilicity due to its electron-donating properties, which may increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and heteroatoms. This complexity can lead to a moderate molecular size, which may affect its permeability. Larger molecules often have lower permeability due to steric hindrance and reduced ability to fit through the membrane.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, which can affect the molecule's solubility and permeability. However, the overall structure, with its multiple aromatic rings, suggests a balance between hydrophilic and lipophilic properties, potentially allowing for moderate permeability.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which may enhance permeability.

7. **Hydration Energy**: The balance of hydrophilic and lipophilic groups suggests that the molecule may have a moderate hydration energy, which can influence its permeability by affecting its interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The combination of lipophilic and polar groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for membrane permeability.

Considering these factors, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between hydrophilic and lipophilic interactions with the artificial membrane.

Final answer: Low-to-moderate permeability

------
# 363

**SMILES:** CC1=C[C@H]([C@@H](C[C@H]1CC2=NC3=C(N2)C=CC(=N3)OC)C(C)C)CNCC4=CC=CC=C4O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the methoxyphenol and the imidazopyridine moiety, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule has a relatively large molecular structure, which includes a cyclohexene ring and a pyrimidine moiety. While size can be a limiting factor for permeability, the presence of rigid aromatic systems may help the molecule maintain a favorable conformation for permeation.

3. **Polarity**: The methoxy group and the hydroxyl group contribute to the polarity of the molecule. However, the overall polarity is balanced by the extensive aromatic system, which may not significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The cyclohexene ring and the aromatic systems contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation.

6. **Aromaticity**: The aromatic rings not only contribute to lipophilicity but also may facilitate interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups like the hydroxyl and methoxy groups may reduce the hydration energy of the molecule, aiding in its permeation through the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Overall, the given molecule's structural features, such as its lipophilicity, rigidity, and balanced polarity, suggest that it would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

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# 364

**SMILES:** CC1=CC(=CC(=C1)NS(=O)(=O)C2=CC3=C(C=C2)NC=C(C3=O)C(=O)NCC4=CC=CO4)C

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with multiple functional groups that can influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the dimethylphenyl and furanyl groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane, as lipophilic compounds tend to dissolve better in lipid environments.

2. **Molecular Size and Weight**: The molecule is relatively large, as indicated by its molecular weight. While size is a factor in permeability, the presence of multiple aromatic rings and a quinoline core may allow for some degree of rigidity, which can help the molecule to permeate more efficiently compared to smaller, more flexible molecules.

3. **Polarity**: The molecule contains a carboxamide group, which can contribute to its polarity. However, the overall polarity is balanced by the lipophilic aromatic rings, suggesting that the molecule may have moderate polarity. This balance can enhance its ability to interact with both the aqueous and lipid phases of the membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the lipid bilayer.

5. **Rigidity**: The quinoline and aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic nature of the molecule can enhance its interaction with the lipid bilayer through π-π interactions, which can further improve its permeability.

7. **Hydration Energy**: The presence of multiple aromatic and heteroaromatic rings suggests that the molecule may have a lower hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to remove water molecules from the surface of the molecule.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it has a balanced affinity for both the aqueous and lipid phases, which is advantageous for permeability in the PAMPA assay.

Overall, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, neutral charge, rigidity, and aromaticity.

Final answer: High permeability

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# 365

**SMILES:** CCCCC(C)/C=C(\C)/C=C(\C)/C(=O)NC1=CC(C2C(C1=O)O2)(/C=C/C=C/C=C/C(=O)NC3=C(CCC3=O)O)O

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple conjugated double bonds and aromatic rings suggests a high degree of lipophilicity. This is likely to enhance the molecule's ability to permeate the lipid-rich artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of multiple conjugated systems and a relatively linear structure might mitigate this effect.

3. **Polarity**: The molecule contains several polar functional groups, such as hydroxyl and carbonyl groups. However, the overall polarity is balanced by the extensive hydrocarbon framework, suggesting moderate polarity. The presence of these groups can facilitate interactions with the aqueous phase, potentially aiding in permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The presence of conjugated double bonds and aromatic rings contributes to a rigid structure, which can enhance membrane permeability by allowing the molecule to maintain a consistent orientation and conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure, with both hydrophilic and hydrophobic regions, suggests a moderate hydration energy. This balance can facilitate its passage through the membrane by allowing it to interact with both the aqueous and lipid environments.

8. **Membrane Affinity**: The molecule's structure, with a mix of hydrophilic and hydrophobic components, suggests a balanced affinity for both phases, which is typically favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and favorable structural rigidity and aromaticity.

Final answer: High permeability

------
# 366

**SMILES:** CC(C)C1=CC=C(C=C1)OCC2=NC3=C(N2CC4=CC=CC=C4)C(=O)N(CCN3)CCOC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of benzyl and phenylmethoxy groups contributes to the lipophilic nature of the molecule. These aromatic groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The imidazo[1,2-a]pyrazinone core is a relatively rigid and compact structure, which may contribute to the molecule's ability to permeate the membrane without significant steric hindrance. However, the overall size of the molecule, including the additional substituents, may still limit its permeability compared to smaller molecules.

3. **Polarity**: The molecule has a low polar surface area due to the absence of multiple polar functional groups. The methoxy and ether groups contribute to the overall polarity, but the presence of aromatic rings and alkyl chains balances this, potentially leading to moderate lipophilicity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The imidazo[1,2-a]pyrazinone core provides a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The benzyl and phenylmethoxy groups introduce aromaticity, which can enhance lipophilicity and influence the molecule's interaction with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of ether and methoxy groups may lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing the energy required to displace water molecules.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 367

**SMILES:** CC(=O)C1=C(N=C(S1)NC(=O)C2=CC=CO2)C3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl group and the furan ring, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 342.38 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and heteroatoms may allow for some flexibility in permeation, depending on the specific interactions with the membrane.

3. **Polarity**: The molecule has a low polar surface area, which is due to the aromatic rings and the acetyl group. This low polarity can enhance its permeability, as it allows the molecule to interact favorably with the hydrophobic lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The presence of aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The molecule's low hydration energy suggests that it can easily transition from an aqueous environment to a lipid environment, enhancing its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous phase and the lipid bilayer, which is advantageous for permeability.

Overall, the given molecule exhibits a combination of lipophilic, rigid, and aromatic characteristics that suggest it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 368

**SMILES:** CCOC1=C(C(=C(C=C1)CCNC(=O)C2=CC3=C(N2CC4=CC=CC=C4)C=CS3)F)OCC

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
To predict the permeability of the given molecule in the Parallel Artificial Membrane Permeability Assay (PAMPA), we need to consider its structural features and how they relate to permeability.

1. **Lipophilicity**: The presence of the 2,4-difluorophenyl group and the ethoxy group contributes to the lipophilic nature of the molecule. These groups increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a thieno[3,2-b]pyrrole core. While the aromatic rings can increase lipophilicity, they also contribute to the molecular size. The balance between these factors will determine the permeability. Typically, larger molecules with multiple rings may have reduced permeability due to size constraints.

3. **Polarity**: The molecule contains a phenyl group with electron-withdrawing fluorine atoms, which can increase its lipophilicity. However, the presence of the ethoxy group and the amide linkage introduces some polarity. The overall polarity is balanced by the lipophilic aromatic rings, suggesting moderate polarity.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The thieno[3,2-b]pyrrole core and the aromatic rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and facilitate interactions with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The given molecule's structure suggests a relatively low hydration energy due to its aromatic and lipophilic components, which can enhance its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups in the molecule suggests it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 369

**SMILES:** COC1=C(C(=C(C=C1)C2=CC3=C(C=C2)N=C(O3)C4=CC=C(C=C4)SC)OC)OC

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methoxy groups on the phenyl ring increases the lipophilicity of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Aromaticity**: The molecule contains multiple aromatic rings, including a phenyl ring and a benzoxazole moiety. Aromatic rings can contribute to the lipophilicity and facilitate interactions with the lipid bilayer, which may enhance permeability.

3. **Molecular Size and Weight**: The overall size of the molecule, due to its multiple aromatic rings and substituents, is relatively large. This could potentially limit its permeability, as larger molecules may have difficulty traversing the membrane.

4. **Polarity**: The methoxy groups and the benzoxazole ring introduce some degree of polarity to the molecule. However, the overall structure is more lipophilic than polar, which suggests that the molecule may still have good permeability due to its ability to interact with the lipid membrane.

5. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

6. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can facilitate its passage through the membrane by reducing the flexibility required for passage.

7. **Hydration Energy**: The presence of methoxy groups and the overall structure may lower the hydration energy of the molecule, making it easier for the molecule to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic interactions in the molecule suggests that it has a favorable affinity for the artificial membrane, which can enhance its permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, aromaticity, and overall balance of hydrophobic and hydrophilic interactions.

Final answer: High permeability

------
# 370

**SMILES:** CC1=CC=C(C=C1)CCNC(=O)C2CCCN(C2)C(=O)C3=CC4=C(N3C)C=CS4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a methyl group and an aromatic phenyl ring in the structure suggests that the molecule has a degree of lipophilicity. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a thiazole ring, which is a heterocyclic compound with nitrogen and sulfur atoms. This contributes to the molecule's polarity. Additionally, the presence of a piperidine ring and a carboxamide group introduces polar functional groups, which can form hydrogen bonds. These features may reduce its permeability due to interactions with the aqueous environment and the membrane.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The thiazole and imidazole rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The phenyl ring and the imidazole ring contribute to the aromatic character of the molecule. Aromaticity can influence lipophilicity and membrane interactions, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups and heteroatoms (such as nitrogen and sulfur) may lead to moderate hydration energy, which can affect the molecule's interaction with the aqueous environment and the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay. The balance of lipophilicity, polarity, and rigidity, along with the presence of aromatic rings, suggests that while it can interact with the membrane, its size and polar functional groups may limit its overall permeability.

Final answer: Low-to-moderate permeability

------
# 371

**SMILES:** CCN1C2=C(C=C1C(=O)N3CCCC(C3)C(=O)NCCC4=CC=C(C=C4)C)SC=C2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a thieno[3,2-b]pyrrole moiety, which is a bicyclic structure containing sulfur and nitrogen, contributes to the lipophilic character of the molecule. Additionally, the 4-ethylphenyl group further enhances lipophilicity due to its hydrophobic aromatic ring. These features suggest that the molecule is likely to have high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular weight and a complex structure, which may limit its permeability due to size constraints. However, the presence of aromatic and heterocyclic rings can provide rigidity, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule contains a piperidine ring, which is a polar, nitrogen-containing heterocycle. However, the overall polar surface area is relatively low due to the dominance of hydrophobic groups, such as the aromatic rings and the thieno[3,2-b]pyrrole moiety. This suggests that the molecule has a low polar surface area, contributing to its permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The bicyclic thieno[3,2-b]pyrrole structure and the aromatic rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl group and the thieno[3,2-b]pyrrole moiety, can influence lipophilicity and molecular interactions with the membrane, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it can easily interact with the lipid bilayer, facilitating permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 372

**SMILES:** CCOC1=C(C=C(C=C1)CCNC(=O)C2=NC3=CC=CC=C3C=C2)OCC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a quinolinecarboxamide, which suggests it has a quinoline core structure linked to a carboxamide group. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of the diethoxyphenyl group indicates that the molecule has increased lipophilicity. This group can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing permeability.

2. **Molecular Size and Weight**: The molecule is relatively small, which is beneficial for permeability as smaller molecules can more easily traverse the membrane.

3. **Polarity**: The carboxamide group introduces some polarity, but the overall structure is dominated by the lipophilic aromatic rings and ethoxy groups, which likely reduce the polar surface area. This suggests that the molecule may have moderate polarity, which can be favorable for permeability.

4. **Charge**: The given molecule is neutral, which is generally favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The quinoline core provides a rigid structure, which can facilitate passage through the membrane by reducing the flexibility and potential for entropic hindrance.

6. **Aromaticity**: The aromatic rings in the quinoline and phenyl groups can enhance lipophilicity and may also participate in π-π interactions with the membrane, potentially aiding in permeability.

7. **Hydration Energy**: The presence of the ethoxy groups and the overall structure may lower the hydration energy, making it easier for the molecule to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is typically favorable for membrane permeability.

Overall, the given molecule's structural features suggest that it would have high permeability in the artificial membrane used in the PAMPA assay.

Final answer: High permeability

------
# 373

**SMILES:** CC1=CC=C(C=C1)OCCN2C3=CC=CC=C3N=C2CCNC(=O)N4CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a member of the benzimidazole class, which is known for its diverse pharmacological properties. Let's analyze the structural features of the given molecule to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of the benzimidazole core and the 4-methylphenoxy group contribute to the lipophilic nature of the molecule. These aromatic and heterocyclic components enhance the molecule's ability to interact with the lipid components of the artificial membrane, suggesting a high degree of lipophilicity.

2. **Molecular Size and Weight**: The overall molecular structure is relatively complex due to the presence of multiple rings and functional groups. However, the benzimidazole core and the piperidine ring contribute to a relatively compact structure, which may not significantly hinder permeability despite the complexity.

3. **Polarity**: The molecule has a low polar surface area due to the absence of multiple polar functional groups. The presence of a carboxamide group introduces some polarity, but the overall structure is dominated by non-polar aromatic and heterocyclic rings, which suggests a low polar surface area.

4. **Charge**: The given molecule is neutral, which is typical for many bioactive compounds. This neutrality allows it to traverse the lipid bilayer more effectively compared to charged molecules.

5. **Rigidity**: The benzimidazole and piperidine rings contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by reducing conformational flexibility, which might otherwise hinder passage through the lipid bilayer.

6. **Aromaticity**: The aromatic benzimidazole and phenyl groups increase the molecule's lipophilicity and may facilitate interactions with the lipid bilayer, enhancing permeability.

7. **Hydration Energy**: The low hydration energy associated with the given molecule's structure suggests that it can easily transition from an aqueous environment to a lipid environment, promoting membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is essential for effective permeation in the PAMPA assay.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 374

**SMILES:** CCOC(=O)C1=CC=C(C=C1)N2C=NC3=C2C=CC(=C3)C(=O)N4CCCCC4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the benzimidazole and benzene moieties, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 434.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and a piperidine moiety may allow for some flexibility and conformational adaptability, which can mitigate the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is primarily due to the aromatic rings and the ester functional group. This low polarity can enhance its ability to interact with the hydrophobic environment of the lipid bilayer, promoting permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings contribute to a degree of rigidity, which can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation during permeation.

6. **Hydration Energy**: The molecule's low hydration energy suggests that it can easily transition from an aqueous environment to a lipid environment, enhancing its permeability.

7. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable affinity for both the aqueous and lipid phases, which is advantageous for permeability.

Overall, the given molecule exhibits a combination of lipophilic, aromatic, and neutral characteristics that suggest it would have high permeability in the PAMPA assay.

Final answer: High permeability

------
# 375

**SMILES:** CC1=CC(=C(N1)C(=O)NC2=CC(=CC=C2)[S+](=O)(N3CCCCCC3)[O-])C

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is an aromatic amide, which suggests it has a certain degree of lipophilicity due to the presence of aromatic rings. Aromatic rings can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

The presence of a pyrrole ring, which is a five-membered heterocyclic aromatic ring, contributes to the molecule's aromatic character. This can further enhance lipophilicity and membrane permeability, as aromatic systems are generally more lipophilic.

The molecule also contains a sulfonyl group attached to a piperidine ring. The sulfonyl group is polar and can form hydrogen bonds, which might influence the molecule's overall polarity and solubility. However, the presence of the piperidine ring, a saturated nitrogen-containing heterocycle, can also contribute to the molecule's basicity and potential for forming hydrogen bonds, which might affect its interaction with the membrane.

The carboxamide group is another polar functional group that can participate in hydrogen bonding. This group can influence the molecule's solubility and permeability by affecting its interaction with the aqueous environment and the lipid bilayer.

Overall, the given molecule's structure suggests a balance between hydrophobic and hydrophilic properties, which is often associated with moderate permeability in PAMPA assays. The aromatic and heterocyclic components contribute to lipophilicity, while the sulfonyl and carboxamide groups introduce polar characteristics. This balance typically results in moderate permeability, neither extremely high nor low. Therefore, the given molecule is likely to exhibit low-to-moderate permeability in the PAMPA assay.

Final answer: Low-to-moderate permeability

------
# 376

**SMILES:** CCOC1=C(C=C(C=C1)CCNC(=O)C2=CC3=CC=CC=C3N2CC4=CC(=CC(=N4)C)C)OCC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the 4-ethoxy-2,6-dimethylphenoxy group contributes to the lipophilic nature of the molecule. This group is an aromatic ether, which can enhance lipophilicity due to its hydrophobic aromatic ring and ethoxy group. Lipophilicity is a key factor in membrane permeability, as it allows the molecule to interact favorably with the lipid bilayer.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings and the indole moiety can help to compact the structure, potentially mitigating this effect.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the absence of multiple polar functional groups. This is further supported by the presence of the indole ring, which is relatively non-polar. The low polar surface area suggests that the molecule can traverse the lipid bilayer with minimal disruption.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The indole moiety and the aromatic rings contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation while interacting with the membrane.

6. **Aromaticity**: The aromatic rings, including the indole and phenyl groups, can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The low hydration energy of the molecule suggests that it is less likely to form strong interactions with water, facilitating its passage through the lipid bilayer.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is essential for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

------
# 377

**SMILES:** CC(C)N(CCC(=O)C1=CC2=CC=CC=C2C=C1)CC3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a member of the naphthalene family, which suggests it has a polycyclic aromatic structure. This structural feature often contributes to lipophilicity, enhancing the molecule's ability to permeate lipid membranes. The presence of a naphthalene moiety indicates that the molecule has a significant hydrophobic character, which is a key factor in its permeability.

The molecule also contains a propan-2-yl group attached to a carbonyl group, forming an aromatic ketone. This functional group can influence the molecule's polarity and hydrogen bonding capabilities. However, the overall structure is dominated by the naphthalene and benzyl groups, which contribute to the molecule's lipophilicity.

The benzyl group attached to the nitrogen atom introduces additional aromaticity, which can further enhance lipophilicity and membrane permeability. The nitrogen atom, being part of an amine, can also participate in hydrogen bonding, but its presence in a relatively bulky group suggests it may not significantly hinder permeability.

Overall, the given molecule's structure, characterized by its aromatic rings and hydrophobic groups, suggests that it would exhibit high permeability in the PAMPA assay due to its lipophilic nature and ability to interact favorably with the lipid components of the artificial membrane.

Final answer: High permeability

------
# 378

**SMILES:** CCOC1=CC=CC=C1CNS(=O)(=O)C2=CC=C(C=C2)C3=CN=C(O3)C4CC4

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a cyclopropyl group and an oxazole ring contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The overall molecular structure is relatively large and complex, which may limit its permeability due to steric hindrance. However, the balance of lipophilic and polar groups can still allow for sufficient permeation.

3. **Polarity**: The sulfonamide group introduces a degree of polarity to the molecule, which can affect its solubility and permeability. The presence of an ethoxy group on the phenyl ring also adds to the polarity, which may reduce permeability compared to a purely hydrophobic molecule.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The oxazole ring and the cyclopropyl group contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The phenyl and oxazole rings introduce aromaticity, which can influence the molecule's lipophilicity and interactions with the membrane. Aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic groups in the molecule suggests that it may have moderate hydration energy, which can influence its permeability by affecting its interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The combination of lipophilic and polar groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability in PAMPA assays.

Considering these structural features, the given molecule is likely to exhibit moderate permeability in the PAMPA assay, balancing between lipophilicity and polarity to interact effectively with the artificial membrane.

Final answer: Low-to-moderate permeability

------
# 379

**SMILES:** CCOC1=C(C=C(C=C1)CCNC(=O)C2=CC3=C(N2C)C=CS3)OCC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thieno[3,2-b]pyrrole moieties, contributes to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a molecular weight of 335.3 g/mol. While size is a factor in permeability, the presence of multiple aromatic rings and a thieno[3,2-b]pyrrole core may allow for some degree of rigidity, which can help in permeating the membrane.

3. **Polarity**: The molecule has a low polar surface area, as indicated by the low number of hydrogen bond donors and acceptors. This low polarity suggests that the molecule is more lipophilic, which can enhance its permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to diffuse through lipid membranes.

5. **Rigidity**: The aromatic rings and the thieno[3,2-b]pyrrole structure contribute to the rigidity of the molecule. This rigidity can facilitate membrane permeation by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic nature of the molecule can influence its interaction with the lipid bilayer, potentially enhancing its permeability due to favorable hydrophobic interactions.

7. **Hydration Energy**: The low hydration energy suggests that the molecule is less likely to form strong interactions with water, which can improve its ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 380

**SMILES:** COC1=CC=CC(=C1O)CNC2=CC=C(C=C2)S(=O)(=O)NC3=CC=CS3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antimicrobial properties. To predict its permeability in the PAMPA assay, we can analyze its structural features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and thiophene groups, contributes to the lipophilic nature of the molecule. This suggests that the given molecule may have a moderate to high lipophilicity, which generally enhances permeability.

2. **Molecular Size and Weight**: The molecule contains several aromatic rings and a sulfonamide group, which contribute to its overall size. While the sulfonamide group is relatively small, the presence of multiple aromatic rings and the thiophene moiety may increase the molecular weight. This could potentially limit permeability, but the overall size is balanced by the lipophilic nature.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic rings. The presence of a methoxy group also adds to the polarity, but the overall polar surface area is relatively low compared to the lipophilic surface area.

4. **Charge**: The given molecule is neutral, which is typical for many sulfonamides. This neutrality allows it to interact favorably with the lipid bilayer of the artificial membrane, enhancing its permeability.

5. **Rigidity**: The aromatic rings and the thiophene moiety contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings, including the phenyl and thiophene groups, can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide and methoxy groups, may lead to moderate hydration energy. However, the overall balance between lipophilicity and polarity suggests that the hydration energy is not a significant barrier to permeability.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typical for compounds with moderate lipophilicity and a balanced polar-lipophilic ratio.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

------
# 381

**SMILES:** CC1=CC(=C(C=C1Cl)OC)NS(=O)(=O)C2=C(N=C3N(C2=O)C=CS3)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a chloro and methoxy group on the phenyl ring, along with a methyl group, suggests that the molecule has a moderate to high lipophilicity. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.3 g/mol. While size is a critical factor in permeability, the presence of multiple rings and functional groups may allow for specific interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The sulfonamide group contributes to the molecule's polarity, which can affect its solubility and permeability. However, the overall polarity is balanced by the lipophilic aromatic and chloro groups, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as it can more easily traverse the lipid bilayer without being repelled by charges.

5. **Rigidity**: The presence of multiple aromatic rings and a thiazolopyrimidine core suggests a degree of rigidity. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings contribute to the lipophilicity and may enhance interactions with the membrane through π-π stacking or hydrophobic interactions, which can improve permeability.

7. **Hydration Energy**: The presence of polar groups like the sulfonamide and the methoxy group may lead to moderate hydration energy, which can influence the molecule's ability to permeate the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and structural features that facilitate membrane interaction.

Final answer: High permeability

------
# 382

**SMILES:** C1=CC=NC(=C1)C2=NC(=CC(=O)N2)CSC3=CC=C(C=C3)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a pyrimidine derivative with several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of a pyrimidinone core suggests a degree of rigidity and planarity, which can facilitate membrane permeation by allowing the molecule to fit snugly into the lipid bilayer. This rigidity can also reduce the molecule's overall flexibility, which can be beneficial for permeability.

The molecule contains a pyridinyl group, which is a nitrogen-containing aromatic ring. Aromatic rings, such as pyridine, can enhance lipophilicity, which generally increases permeability. However, the pyridinyl group also introduces some polarity due to the nitrogen atom, which may slightly reduce overall lipophilicity.

Additionally, the molecule has a 4-chlorophenyl group attached via a thioether linkage. The chlorophenyl group contributes to the lipophilicity due to the aromatic ring and the chlorine atom, which is relatively non-polar. The thioether linkage (sulfur atom) can also influence the molecule's electronic properties and lipophilicity, potentially enhancing permeability.

The overall structure of the given molecule suggests a balance between lipophilicity and polarity, with the pyrimidinone core providing rigidity and the aromatic and chlorinated groups enhancing lipophilicity. These features collectively suggest that the given molecule would exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 383

**SMILES:** CCOC1=C(C=C(C=C1)CCNC(=O)C2=CC=NN2CC3=CC=CC(=C3)C)OCC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the 3,4-dimethoxyphenyl group and the ethyl group attached to the phenyl ring contribute to the lipophilic nature of the molecule. These groups increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic rings and the ethyl group may help to maintain a balance, allowing for sufficient permeability.

3. **Polarity**: The molecule contains polar functional groups such as the carboxamide and the ethoxy group. However, the overall polar surface area is relatively low due to the dominance of the lipophilic aromatic and alkyl groups. This suggests that the molecule may have moderate polarity, which can influence its interaction with the artificial membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The presence of aromatic rings contributes to the rigidity of the molecule. This rigidity can enhance the ability of the molecule to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic rings in the structure can engage in π-π interactions with the lipid bilayer, which may enhance permeability. However, this also depends on the balance with the lipophilic and polar characteristics of the molecule.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy due to the presence of non-polar groups, which can facilitate membrane permeation.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a moderate affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, moderate polarity, and balanced structural features that facilitate interaction with the artificial membrane.

Final answer: High permeability

------
# 384

**SMILES:** C1=CC=C(C(=C1)CS(=O)(=O)C2=NC=C(C(=N2)C(=O)NC3=CC=CC=C3F)Cl)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyrimidine rings, contributes to the lipophilic nature of the molecule. Additionally, the presence of halogen atoms like chlorine and fluorine can enhance lipophilicity due to their electron-withdrawing properties, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains polar functional groups such as the sulfonamide and amide groups. These groups can form hydrogen bonds, which may increase the molecule's affinity for the aqueous phase and reduce its overall lipophilicity. However, the balance between these polar and non-polar regions will determine the overall permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The aromatic rings contribute to the rigidity of the molecule, which can enhance its ability to permeate the membrane by maintaining a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can also participate in π-π interactions with the lipid bilayer, which may enhance permeability by stabilizing the molecule within the membrane.

7. **Hydration Energy**: The presence of halogen atoms and aromatic rings suggests that the hydration energy of the molecule is relatively low, which can facilitate its permeation through the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity, which facilitate its interaction and passage through the artificial membrane.

Final answer: High permeability

------
# 385

**SMILES:** CCCC1=NC2=C(C=CC(=C2)C(=O)NC3CCCCC3)SC4=C1C=C(C=C4)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a dibenzothiazepine, which is a tricyclic compound containing a thiazepine ring fused with two benzene rings. This structural framework is known for its potential biological activity, often associated with central nervous system effects.

Analyzing the properties of the given molecule:

1. **Lipophilicity**: The presence of aromatic rings and the cyclohexyl group contribute to the lipophilic nature of the molecule. This suggests that the molecule may have a high lipophilicity, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The tricyclic structure and the attached functional groups, such as the carboxamide, contribute to a relatively large molecular size. While size can be a limiting factor for permeability, the specific arrangement of the rings and substituents may still allow for sufficient permeation.

3. **Polarity**: The carboxamide group introduces some polarity, but the overall structure is dominated by the lipophilic aromatic rings. This balance suggests moderate polarity, which can facilitate membrane permeability without being too high to hinder it.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The tricyclic structure imparts a degree of rigidity, which can enhance the ability of the molecule to permeate the membrane by maintaining a consistent conformation that interacts favorably with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability by stabilizing the interaction with the membrane.

7. **Hydration Energy**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it may have a moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous environment.

8. **Membrane Affinity**: The combination of lipophilic and polar characteristics suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typically favorable for membrane permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

------
# 386

**SMILES:** CC1CCN(CC1)S(=O)(=O)C2=CC3=C(C=C2)N(C(=O)C=C3)CC(=O)NCC4=CC=C(C=C4)Cl

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the chlorophenyl group and the quinoline moiety, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of aromatic rings can help to some extent by providing a more rigid structure that might facilitate passage through the membrane.

3. **Polarity**: The molecule contains several polar groups, including the sulfonyl group attached to the piperidine ring and the acetamide linkage. These polar groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but could also hinder permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The quinoline and chlorophenyl groups contribute to the rigidity of the molecule, which can improve its ability to permeate the membrane by reducing flexibility and allowing a more defined interaction with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can affect its permeability. Lower hydration energy generally improves membrane permeation, but the overall balance of polar and non-polar regions will dictate the outcome.

8. **Membrane Affinity**: The molecule's structure suggests a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability in PAMPA assays.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic aromatic rings, neutral charge, and balanced polarity. However, the large size and presence of polar groups may limit its permeability to some extent.

Final answer: High permeability

------
# 387

**SMILES:** C1COC2=C(C=C(C=C2)C3=CN=C(S3)N4CCC(CC4)C(=O)NC5=CC=CC=C5)OC1

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperidinecarboxamide, which is a type of compound known for its potential biological activity. Let's analyze its structural features to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of a benzodioxepin moiety, which is a cyclic ether, contributes to the lipophilic character of the molecule. Additionally, the thiazole ring and phenyl group further enhance lipophilicity. These features suggest that the molecule is likely to have a high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule contains several aromatic and heterocyclic rings, which contribute to its molecular size and weight. While the size of the molecule is relatively large, the presence of multiple rings can also introduce rigidity, which may help in permeating the membrane more efficiently.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and heterocycles, which are non-polar. The thiazole ring and the piperidine ring introduce some degree of polarity, but overall, the molecule is expected to have a low polar surface area, contributing to higher permeability.

4. **Charge**: The molecule is neutral, which is typical for many bioactive compounds. This neutrality allows it to interact favorably with the lipid bilayer of the artificial membrane, enhancing its permeability.

5. **Rigidity**: The aromatic and heterocyclic rings impart a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing the flexibility and conformational changes required for permeation.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl group and the thiazole ring, can influence the molecule's interaction with the lipid bilayer, potentially enhancing its permeability through hydrophobic interactions.

7. **Hydration Energy**: The low hydration energy associated with the molecule's structure suggests that it can easily interact with the lipid bilayer, enhancing its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a favorable membrane affinity, which is beneficial for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay.

Final answer: High permeability

------
# 388

**SMILES:** CCCC1=NC2=C(C=CC(=C2)C(=O)NC3CCCC3)SC4=C1C=C(C=C4)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a dibenzothiazepine, which is a tricyclic compound containing a thiazepine ring fused with two benzene rings. This structural framework is known for its potential biological activity, often associated with central nervous system effects.

Analyzing the properties of the given molecule:

1. **Lipophilicity**: The presence of aromatic rings and the dibenzothiazepine core contribute to the lipophilic nature of the molecule. This lipophilicity is likely to enhance its ability to permeate lipid membranes, suggesting high permeability.

2. **Molecular Size and Weight**: The tricyclic structure of the dibenzothiazepine core, along with the propyl and cyclopentyl groups, contributes to a relatively large molecular size. However, the overall size is balanced by the relatively small number of atoms, which may still allow for sufficient permeability through the artificial membrane.

3. **Polarity**: The carboxamide group introduces some polarity, but the overall structure is dominated by the hydrophobic aromatic rings, which likely outweigh the polar contributions. This suggests moderate polarity, which can still support permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The tricyclic structure imparts a degree of rigidity, which can facilitate membrane permeation by allowing the molecule to maintain a consistent conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings contribute to the lipophilicity and may also participate in π-π interactions with the lipid bilayer, enhancing permeability.

7. **Hydration Energy**: The presence of both hydrophobic and hydrophilic groups suggests that the molecule may have a moderate hydration energy, which can influence its interaction with the membrane and its permeability.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, the given molecule is likely to exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA) due to its lipophilic nature, balanced polarity, and structural features that facilitate membrane interaction.

Final answer: High permeability

------
# 389

**SMILES:** CC1=NN2CCCN(C2=C1C3=CC=CC=C3OCC4=CC=CC=C4)C(=O)CC5=CC6=C(C=C5)OCO6

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and benzodioxole groups, contributes to the lipophilic nature of the molecule. These aromatic systems can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule is relatively large and complex, which may limit its permeability due to steric hindrance. Larger molecules often have reduced permeability as they may not fit easily through the membrane pores.

3. **Polarity**: The molecule contains a dioxole moiety, which can contribute to its polarity. However, the overall structure is dominated by aromatic and hydrocarbon components, suggesting that the molecule is more lipophilic than polar.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The presence of multiple aromatic rings and a pyrazolo-pyridine core imparts a degree of rigidity to the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic systems in the molecule can enhance its lipophilicity and may also participate in π-π interactions with the membrane, potentially aiding in permeation.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can enhance its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, aromaticity, and balanced polarity.

Final answer: High permeability

------
# 390

**SMILES:** COC1=CC(=C(C=C1)OC)C2=NN=C3N2N=C(CS3)C4=C(C=CC=C4OC)OC

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex heterocyclic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple methoxy groups on the phenyl rings increases the lipophilicity of the molecule. Methoxy groups are electron-donating and can enhance the hydrophobic character of the molecule, which generally increases permeability.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively large and complex, which may limit its permeability due to steric hindrance. However, the specific arrangement of the phenyl and triazolo-thiadiazine rings may allow for some flexibility and conformational adaptability, which can help in permeating the membrane.

3. **Polarity**: The methoxy groups contribute to the polarity of the molecule, but the overall effect is balanced by the lipophilic aromatic rings. The low polar surface area and the presence of few hydrogen bond donors/acceptors suggest moderate polarity, which can favor permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The triazolo-thiadiazine core provides a degree of rigidity, which can enhance the ability of the molecule to interact with the lipid bilayer, potentially improving permeability.

6. **Aromaticity**: The aromatic rings contribute to the lipophilicity and may facilitate interactions with the lipid bilayer through π-π interactions, which can enhance permeability.

7. **Hydration Energy**: The presence of methoxy groups and the overall structure suggest a lower hydration energy, which can improve membrane permeation by reducing the energy required to disrupt the water layer surrounding the molecule.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties, along with the structural features, suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, structural rigidity, and membrane affinity.

Final answer: High permeability

------
# 391

**SMILES:** CCN1C(=NN=N1)SC2=NC=NC3=C2C(=CS3)C4=CC=C(C=C4)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex structure that includes several key features influencing its permeability in the PAMPA assay. Let's break down these features:

1. **Lipophilicity**: The presence of a thienopyrimidine core and a 4-methylphenyl group suggests a significant degree of lipophilicity. These aromatic and heterocyclic components contribute to the molecule's ability to interact with the lipid components of the artificial membrane, enhancing its permeability.

2. **Molecular Size and Weight**: The overall size of the molecule, including the tetrazole and thienopyrimidine rings, is relatively large. While size is a factor in permeability, the presence of multiple aromatic and heterocyclic rings can also facilitate interactions with the membrane, potentially offsetting the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area due to the presence of aromatic rings and the absence of multiple polar functional groups. This low polarity enhances its ability to permeate the lipid-rich environment of the artificial membrane.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid bilayers.

5. **Rigidity**: The aromatic and heterocyclic rings contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The presence of aromatic rings, such as the phenyl and thienopyrimidine groups, can enhance lipophilicity and facilitate interactions with the membrane, potentially increasing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests a favorable membrane affinity, which is conducive to high permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, rigidity, and balanced polarity.

Final answer: High permeability

------
# 392

**SMILES:** CCOC(=O)C1CCN(CC1)C(=O)C(C)(C)NC(=O)NC2=CC=C(C=C2)C3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound that can be analyzed based on its structural features to predict its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the biphenyl moiety (4-phenylphenyl), contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer, suggesting high permeability.

2. **Molecular Size and Weight**: The molecule is relatively large, with a significant number of atoms and functional groups. While size can be a limiting factor for permeability, the presence of aromatic rings and the overall structure may still allow for sufficient permeation.

3. **Polarity**: The molecule contains several polar functional groups, including ester and amide linkages. However, the overall polar surface area is balanced by the lipophilic aromatic rings, suggesting moderate polarity. This balance can contribute to moderate permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules typically have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the piperidine ring contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The biphenyl structure is a significant contributor to the molecule's lipophilicity and potential for π-π interactions with the lipid bilayer, which can enhance permeability.

7. **Hydration Energy**: The presence of polar groups and the overall structure suggest that the molecule may have moderate hydration energy, which can influence its permeability by affecting its solubility and interaction with the aqueous phase.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Overall, considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

------
# 393

**SMILES:** CC1=C(N(C(=C1C(=O)C)C)C)C(=O)NC2=CC(=CC=C2)[S+](=O)(N3CCCCCC3)[O-]

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of acetyl and phenyl groups contributes to the lipophilic nature of the molecule. These groups can enhance the molecule's ability to interact with the lipid components of the artificial membrane, potentially increasing its permeability.

2. **Molecular Size and Weight**: The molecule contains a pyrrole ring with additional methyl groups, which may contribute to a moderate molecular size. While the size is not excessively large, it may still limit permeability due to steric hindrance.

3. **Polarity**: The amide linkage and the presence of a sulfonyl group introduce some degree of polarity. However, the overall structure is dominated by the lipophilic aromatic and acetyl groups, suggesting that the molecule's polarity is not high enough to significantly hinder permeability.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The pyrrole ring and aromatic phenyl group contribute to the rigidity of the molecule. This rigidity can facilitate passage through the membrane by allowing the molecule to maintain a stable conformation.

6. **Aromaticity**: The aromatic rings enhance lipophilicity and may also participate in π-π interactions with the membrane, potentially aiding in permeability.

7. **Hydration Energy**: The presence of both hydrophobic and hydrophilic groups suggests that the molecule has a balanced affinity for both phases, which can favor membrane permeation.

8. **Membrane Affinity**: The combination of lipophilic and polar groups suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Overall, the given molecule's structural features, such as its lipophilicity, moderate size, and balanced polarity, suggest that it would exhibit high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

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# 394

**SMILES:** CCOC1=CC=CC=C1N(CC(=O)NC2=C(C=CC(=C2)OC)OC)S(=O)(=O)C3=CC=CC=C3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a sulfonamide, which is a class of compounds known for their antibacterial properties. To predict its permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA), we can analyze its structural features based on the properties mentioned.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl groups and the methoxyphenyl group, contributes to the lipophilic nature of the molecule. This suggests that the given molecule may have a relatively high lipophilicity, which generally correlates with increased permeability.

2. **Molecular Size and Weight**: The given molecule is relatively complex, with multiple aromatic rings and a sulfonamide group. While the sulfonamide group itself is not large, the overall molecular size and weight may limit permeability due to steric hindrance.

3. **Polarity**: The sulfonamide group introduces some degree of polarity, but the overall structure is dominated by the lipophilic aromatic rings. The methoxy groups also contribute to the molecule's polarity, but the overall polar surface area is relatively low compared to the lipophilic surface area.

4. **Charge**: The given molecule is neutral, which is typical for sulfonamides. This neutrality allows it to interact favorably with the lipid bilayer of the artificial membrane, enhancing its permeability.

5. **Rigidity**: The aromatic rings provide a degree of rigidity to the molecule, which can facilitate its passage through the membrane by reducing the flexibility required for diffusion.

6. **Aromaticity**: The presence of multiple aromatic rings can enhance lipophilicity and influence the molecule's ability to interact with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of polar groups, such as the sulfonamide and methoxy groups, may lead to moderate hydration energy. This can affect the molecule's ability to permeate the membrane, but the overall balance of lipophilicity and polarity suggests that the hydration energy is not a significant limiting factor.

8. **Membrane Affinity**: The given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typical for compounds with moderate polarity and significant lipophilicity. This balance suggests that the molecule would exhibit good permeability in the PAMPA assay.

In summary, the given molecule's structural features, including its lipophilicity, aromaticity, and balanced polarity, suggest that it would have high permeability in the PAMPA assay.

Final answer: High permeability

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# 395

**SMILES:** CCCC1=C(C2=C(O1)C=CC(=C2)NS(=O)(=O)C3=CC=C(C=C3)OC)C(=O)OCC

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of the methoxyphenyl group and the propyl chain contribute to the lipophilic nature of the molecule. These groups increase the overall hydrophobic character, which generally enhances permeability through lipid membranes.

2. **Molecular Size and Weight**: The benzofuran core and the various substituents, including the ethyl ester and the sulfamoyl group, contribute to a relatively large molecular size. While size can be a limiting factor for permeability, the specific arrangement and connectivity of these groups may still allow for sufficient permeation.

3. **Polarity**: The sulfamoyl group introduces some degree of polarity, which can affect the molecule's solubility and interaction with the membrane. However, the overall structure is balanced with hydrophobic groups, suggesting moderate polarity.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often face difficulties in crossing lipid bilayers due to their interaction with the polar head groups of the membrane.

5. **Rigidity**: The benzofuran core provides a degree of rigidity, which can facilitate passage through the membrane by maintaining a consistent orientation and conformation.

6. **Aromaticity**: The benzofuran and methoxyphenyl groups introduce aromaticity, which can enhance lipophilicity and influence interactions with the lipid bilayer, potentially aiding in permeability.

7. **Hydration Energy**: The presence of polar groups like the sulfamoyl and ester may lead to moderate hydration energy, which can affect the molecule's interaction with water and the membrane.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic groups suggests that the molecule has a balanced affinity for both the aqueous and lipid phases, which is generally favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its balanced lipophilicity, moderate polarity, and favorable molecular interactions with the artificial membrane.

Final answer: High permeability

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# 396

**SMILES:** CCOC1=CC=C(C=C1)NC(=O)CC2C(=O)N(C(=O)N2CCC3=C(C=CS3)C)C4=CC=C(C=C4)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the 4-ethoxyphenyl and the thiophene ring, contributes to the lipophilic nature of the molecule. The ethoxy group further enhances lipophilicity, which generally increases permeability up to a certain threshold.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of multiple rings and functional groups can create a balance that allows for sufficient permeability.

3. **Polarity**: The molecule has a low polar surface area due to the presence of non-polar aromatic rings and the ethoxy group. This low polarity contributes to higher permeability as it allows the molecule to interact favorably with the lipid bilayer.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often face difficulties in crossing lipid membranes.

5. **Rigidity**: The presence of aromatic rings and the imidazolidine-2,4-dione core provides a degree of rigidity, which can enhance membrane permeability by allowing the molecule to maintain a stable conformation as it interacts with the membrane.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The molecule's structure suggests a relatively low hydration energy, which facilitates its passage through the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests a favorable membrane affinity, which is essential for high permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its favorable balance of lipophilicity, rigidity, and membrane affinity.

Final answer: High permeability

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# 397

**SMILES:** COC1=CC=CC(=C1)C2=CSC(=N2)N3CCC(CC3)C(=O)N

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a piperidinecarboxamide, which is characterized by a piperidine ring attached to a carboxamide group. This structure suggests that the molecule has a certain degree of flexibility and potential for hydrogen bonding, which can influence its permeability.

The presence of a thiazole ring, which is a heterocyclic compound containing both sulfur and nitrogen, contributes to the molecule's aromaticity and potential for electronic interactions. This can enhance the molecule's lipophilicity, aiding in its permeability through the lipid bilayer.

The methoxyphenyl group introduces additional aromatic character and lipophilicity, which can further improve the molecule's ability to permeate the membrane. The methoxy group can also participate in hydrophobic interactions, which may enhance the molecule's affinity for the lipid phase.

The piperidine ring is a saturated heterocycle, which provides a degree of flexibility and can influence the molecule's overall conformation. This flexibility can be beneficial for navigating the membrane, as it allows the molecule to adapt its shape to fit into the lipid bilayer.

Overall, the given molecule's combination of aromatic rings, heterocyclic components, and functional groups suggests that it has a balanced lipophilicity and structural flexibility, which are conducive to high permeability in the PAMPA assay.

Final answer: High permeability

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# 398

**SMILES:** CC1=CC(=C(C=C1)NC(=O)C2=C(C3=C(N2C)C=CC(=C3)C)N4CCCC4=O)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is an aromatic amide, which suggests it has a complex structure with both aromatic and amide functional groups. Let's analyze its properties to predict its permeability:

1. **Lipophilicity**: The presence of multiple methyl groups on the pyrroloindole and dimethylphenyl rings indicates a high degree of lipophilicity. This suggests that the molecule is likely to have good permeability due to its ability to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The structure includes a pyrroloindole core, which is relatively rigid and compact. This rigidity can help the molecule to permeate the membrane more efficiently compared to more flexible or larger molecules.

3. **Polarity**: The amide group contributes to the polarity of the molecule, but the overall structure is dominated by non-polar aromatic rings, which suggests that the molecule has a low polar surface area. This indicates that the molecule is likely to have good permeability as it can traverse the lipid bilayer with minimal disruption.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The pyrroloindole structure provides a rigid framework, which can enhance the molecule's ability to permeate the membrane by reducing the energy required for conformational changes.

6. **Aromaticity**: The aromatic rings in the structure can interact with the lipid bilayer through π-π interactions, which can further enhance permeability.

7. **Hydration Energy**: The presence of hydrophobic groups and aromatic rings suggests that the molecule has a lower hydration energy, which is beneficial for membrane permeation as it reduces the energy required to remove water molecules from the molecule's surface.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is typically favorable for permeability.

Overall, the given molecule's structural features, such as its lipophilicity, rigidity, aromaticity, and balanced polarity, suggest that it would have high permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA).

Final answer: High permeability

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# 399

**SMILES:** CC1=C([C@H](C(=C(N1)C)C(=O)O[C@@H]2CCCN(C2)CC3=CC=CC=C3)C4=CC(=CC=C4)[N+](=O)[O-])C(=O)OC.Cl

**Label:** 1

**Predi:** 0

**Correct:** 0

# Response:
The given molecule is a dihydrochloride salt, which indicates the presence of two chloride ions. This suggests that the molecule is likely to be charged, which can affect its permeability. Charged molecules generally have lower permeability through lipid membranes due to their inability to diffuse through the hydrophobic lipid bilayer.

The presence of aromatic rings, such as the benzyl and nitrophenyl groups, contributes to the molecule's lipophilicity. Aromatic rings can enhance lipophilicity, which may improve permeability up to a certain extent. However, the overall effect will depend on the balance between lipophilicity and the molecule's size and charge.

The piperidine ring in the structure adds to the molecule's complexity and may influence its rigidity and conformation. The rigidity can affect how the molecule interacts with the lipid bilayer, potentially improving permeability if the molecule can maintain a favorable orientation.

The ester groups in the molecule, indicated by the dihydroxy and methoxy components, suggest that the molecule has polar characteristics. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but could also hinder permeability through the lipid bilayer due to the polar nature of the interactions.

Overall, the given molecule's charged nature, combined with its aromatic and polar characteristics, suggests that it may have low-to-moderate permeability in the PAMPA assay. The balance between lipophilicity and polar interactions, along with the structural features, likely results in a moderate ability to permeate the artificial membrane.

Final answer: Low-to-moderate permeability

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# 400

**SMILES:** CC1=CC(=CC=C1)N2C=NC3=C2C=CC(=C3)C(=O)N4CCCC(C4)C(F)(F)F

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of a benzimidazole moiety and a trifluoromethyl group contribute to the lipophilic nature of the molecule. The trifluoromethyl group is particularly known for enhancing lipophilicity due to its strong electron-withdrawing properties and ability to increase the hydrophobic character of the molecule.

2. **Molecular Size and Weight**: The given molecule is relatively large, with a molecular weight of 384.5 g/mol. While size is a factor in permeability, the presence of aromatic rings and a piperidine ring can help to maintain a certain degree of rigidity, which may mitigate the negative effects of size.

3. **Polarity**: The molecule has a low polar surface area, which is indicative of its overall non-polar character. This is due to the presence of aromatic rings and the trifluoromethyl group, which are non-polar. The low polar surface area suggests that the molecule would have higher permeability.

4. **Charge**: The molecule is neutral, which is beneficial for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The benzimidazole and piperidine rings contribute to the rigidity of the molecule. This rigidity can enhance the molecule's ability to permeate the membrane by reducing the flexibility and conformational changes required for passage.

6. **Aromaticity**: The benzimidazole and phenyl rings contribute to the aromatic character of the molecule. Aromaticity can influence lipophilicity and the ability of the molecule to interact with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of the trifluoromethyl group and aromatic rings suggests that the molecule has a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to overcome the hydration shell.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests that it has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these structural features, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

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# 401

**SMILES:** CCN(CC)C(=O)C1=COC(=N1)COC2=CC3=C(CCN(C3C4=CC(=CC=C4)F)C(=O)C(C)C)C=C2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and isoquinoline groups, contributes to the lipophilic nature of the molecule. The fluorine substitution on the phenyl ring can enhance lipophilicity due to the strong electronegativity of fluorine, which can increase the molecule's ability to interact with the lipid membrane.

2. **Molecular Size and Weight**: The molecule is relatively large, which may limit its permeability due to steric hindrance. However, the presence of multiple rings and functional groups can create a balance between size and permeability.

3. **Polarity**: The molecule contains several polar groups, including the carbonyl groups in the isoquinoline and carboxamide moieties. These groups can form hydrogen bonds, which may enhance solubility in the aqueous phase but could also hinder permeability through the lipid bilayer.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the isoquinoline structure contribute to the rigidity of the molecule. Rigidity can enhance membrane permeability as it allows the molecule to maintain a stable conformation when interacting with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups suggests that the molecule may have moderate hydration energy, which can affect its interaction with the aqueous and lipid phases.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic regions in the molecule suggests it has a balanced affinity for both phases, which is generally favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, balanced polarity, and structural rigidity.

Final answer: High permeability

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# 402

**SMILES:** CCC1=CC=CC=C1N2C(=N)C3=C(NN=C3N=C2SCC(=O)NC4=CC=C(C=C4)C)C

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several distinct structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of multiple aromatic rings, such as the phenyl groups and the pyrrolo[2,3-d]pyrimidine core, suggests that the given molecule is relatively lipophilic. This lipophilicity is likely to enhance its permeability through the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a relatively large molecular structure due to its multiple rings and substituents. While size can be a limiting factor for permeability, the presence of aromatic systems and the overall rigidity of the structure may help it permeate the membrane more efficiently compared to smaller, more flexible molecules.

3. **Polarity**: The molecule contains a thioether linkage (sulfanyl group) and an imino group, which contribute to its polar characteristics. However, the overall polar surface area is relatively low due to the dominance of aromatic and hydrocarbon components, which may still allow for sufficient permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often face significant barriers in crossing lipid membranes.

5. **Rigidity**: The pyrrolo[2,3-d]pyrimidine core and the aromatic rings contribute to the rigidity of the molecule. This rigidity can enhance its ability to interact with the lipid bilayer, potentially improving its permeability.

6. **Aromaticity**: The aromatic rings in the structure can engage in π-π interactions with the lipid bilayer, which may further facilitate permeation.

7. **Hydration Energy**: The presence of hydrophobic and aromatic groups suggests that the given molecule has a lower hydration energy, which can enhance its ability to traverse the membrane by reducing its affinity for water.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic components in the given molecule suggests that it has a favorable membrane affinity, which is conducive to high permeability.

Considering these structural characteristics, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilicity, rigidity, and balanced polarity.

Final answer: High permeability

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# 403

**SMILES:** C1CN(CC2=CN=C(C=C2N1)NC3=CC=CC=C3)CC4=CC(=CC=C4)F

**Label:** 0

**Predi:** 1

**Correct:** 0

# Response:
The given molecule is a pyridopyridine derivative with several functional groups and structural features that influence its permeability in the PAMPA assay.

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine groups, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane, as lipophilic compounds tend to dissolve better in lipid environments.

2. **Molecular Size and Weight**: The overall structure of the given molecule is relatively complex, with multiple rings and substituents. While the pyridopyridine core is relatively planar, the additional phenyl and pyridine groups, along with the fluorophenyl substituent, increase the molecular size. This could potentially limit its permeability due to steric hindrance, but the aromatic nature may still favor permeability.

3. **Polarity**: The molecule contains several nitrogen atoms, which can contribute to its polarity. However, the overall polar surface area is relatively low due to the dominance of aromatic rings, which are non-polar. This suggests that the molecule may have moderate polarity, which can affect its permeability.

4. **Charge**: The given molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The aromatic rings and the pyridopyridine core provide a degree of rigidity to the molecule. This rigidity can facilitate passage through the membrane by maintaining a consistent orientation and reducing flexibility, which might otherwise hinder permeation.

6. **Aromaticity**: The aromatic nature of the molecule, with multiple rings, can enhance its lipophilicity and influence its interaction with the lipid bilayer, potentially improving permeability.

7. **Hydration Energy**: The presence of fluorine in the fluorophenyl group can lower the hydration energy of the molecule, making it easier for the molecule to traverse the membrane by reducing its affinity for water.

8. **Membrane Affinity**: The balance of hydrophobic and hydrophilic properties in the given molecule suggests it has a favorable membrane affinity, which can enhance its permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its lipophilic nature, aromaticity, and balanced polarity, despite its relatively large size and complex structure.

Final answer: High permeability

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# 404

**SMILES:** C1=COC(=C1)CNC(=O)COC(=O)CCC(=O)C2=CC=CS2

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex ester that includes several functional groups and structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of furan rings, which are aromatic and contribute to the molecule's overall lipophilicity, suggests that the given molecule is likely to have a moderate to high lipophilicity. This is because aromatic rings can enhance the ability of the molecule to interact with the lipid components of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule is relatively large, with multiple functional groups and rings. While size can be a limiting factor for permeability, the presence of aromatic rings and ester linkages may help to maintain a balance that allows for sufficient permeability.

3. **Polarity**: The ester linkage and the presence of carbonyl groups introduce some degree of polarity. However, the overall structure is dominated by the lipophilic furan rings, which may outweigh the polar effects, leading to moderate lipophilicity.

4. **Charge**: The given molecule is neutral, which is beneficial for permeability as charged molecules typically have lower permeability due to their inability to diffuse through the hydrophobic lipid bilayer.

5. **Rigidity**: The aromatic furan rings contribute to the rigidity of the molecule. Rigidity can enhance permeability as it allows the molecule to maintain a stable conformation when interacting with the membrane.

6. **Aromaticity**: The furan rings also contribute to the aromatic character of the molecule, which can influence its interaction with the lipid bilayer, potentially enhancing permeability.

7. **Hydration Energy**: The presence of polar groups, such as the ester and carbonyl groups, may lead to moderate hydration energy. However, the overall structure is likely to have a lower hydration energy due to the dominance of lipophilic furan rings.

8. **Membrane Affinity**: The balance of lipophilic and polar groups suggests that the given molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is favorable for permeability.

Considering these factors, the given molecule is likely to exhibit high permeability in the PAMPA assay due to its moderate lipophilicity, neutral charge, and balanced structural features that facilitate interaction with the artificial membrane.

Final answer: High permeability

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# 405

**SMILES:** CC1=CC=CC2=NC(=C(N12)NC3=CC=C(C=C3)C(C)C)C4=CN=CC=C4

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is a complex organic compound with several structural features that influence its permeability in the PAMPA assay. Let's analyze these features:

1. **Lipophilicity**: The presence of aromatic rings, such as the phenyl and pyridine rings, contributes to the lipophilic nature of the molecule. This can enhance its ability to permeate the lipid bilayer of the artificial membrane.

2. **Molecular Size and Weight**: The given molecule has a moderate molecular size and weight, which is typical for many bioactive compounds. While larger molecules can have reduced permeability due to size constraints, the specific structure of this molecule suggests it may still have sufficient permeability.

3. **Polarity**: The molecule contains a pyridine ring, which is polar, and an amine group, which can act as a hydrogen bond donor and acceptor. However, the overall polar surface area is relatively low due to the presence of multiple aromatic rings, which are non-polar. This balance of polar and non-polar regions can facilitate membrane permeation.

4. **Charge**: The molecule is neutral, which is favorable for permeability as charged molecules often have reduced ability to cross lipid membranes.

5. **Rigidity**: The presence of multiple aromatic rings contributes to the rigidity of the molecule. This rigidity can enhance its ability to permeate the membrane by allowing it to maintain a stable conformation as it interacts with the lipid bilayer.

6. **Aromaticity**: The aromatic rings can engage in π-π interactions with the lipid bilayer, which can further enhance permeability.

7. **Hydration Energy**: The balance of polar and non-polar regions in the molecule suggests that it may have a lower hydration energy, which can improve its ability to permeate the membrane by reducing the energy required to transition from an aqueous to a lipid environment.

8. **Membrane Affinity**: The combination of lipophilic and polar features suggests that the molecule has a balanced affinity for both the aqueous phase and the lipid bilayer, which is generally favorable for permeability.

Overall, the given molecule exhibits a combination of lipophilic and polar characteristics, a moderate size, and a stable, rigid structure, all of which contribute to its ability to permeate the artificial membrane in the PAMPA assay. Therefore, the permeability of the given molecule is likely to be classified as high.

Final answer: High permeability

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# 406

**SMILES:** CN1CCC2=CC3=C(C=C2C1)OCO3

**Label:** 1

**Predi:** 1

**Correct:** 1

# Response:
The given molecule is characterized by several structural features that influence its permeability in the PAMPA assay. 

Firstly, the presence of aromatic rings, such as the isoquinoline moiety, contributes to the molecule's lipophilicity. Aromatic rings can enhance the ability of the molecule to interact with the lipid components of the artificial membrane, potentially increasing its permeability. However, the balance between lipophilicity and other factors will determine the overall permeability.

Secondly, the dioxole ring introduces an ether linkage, which can affect the molecule's polarity and hydrogen bonding potential. While ethers generally contribute to lipophilicity, the presence of oxygen atoms can also introduce some degree of polarity, which may influence the molecule's interaction with the membrane.

The methyl group attached to the aromatic system can further modulate lipophilicity, potentially enhancing the molecule's ability to permeate the membrane by increasing its hydrophobic character.

Additionally, the molecule's overall structure, including the fused ring system, suggests a degree of rigidity. This rigidity can facilitate passage through the membrane by reducing the energy required for conformational changes during permeation.

The combination of these features suggests that the given molecule likely exhibits high permeability in the PAMPA assay, as it possesses a balance of lipophilicity, aromaticity, and structural rigidity conducive to membrane permeation.

Final answer: High permeability

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