Quantitative Structure-Activity Relationships (QSAR) PDF

Quantitative Structure-Activity Relationships (QSAR) Patrick Chapter 18 2. Hydrophobicity of Substituents: substituent hydrophobicity constant (π) A measure of a substituent’s hydrophobicity relative to hydrogen Tabulated values exist for aliphatic and aromatic substituents Measured experimentally b...

Quantitative Structure-Activity Relationships (QSAR) Patrick Chapter 18 2. Hydrophobicity of Substituents: substituent hydrophobicity constant (π) A measure of a substituent’s hydrophobicity relative to hydrogen Tabulated values exist for aliphatic and aromatic substituents Measured experimentally by comparison of log P values with log P of parent structure Cl CONH2 Example: Benzene (Log P = 2.13) Chlorobenzene (Log P = 2.84) Cl = 0.71 Benzamide (Log P = 0.64) CONH = -1.49 Group CH3 t-Bu OH OCH3 CF3 π (aliphatic subsituents) 0.50 1.68 -1.16 0.47 π (aromatic subsituents) 0.52 1.68 -0.67 -0.02 2 Cl Br F 1.07 0.39 0.60 -0.17 1.16 0.71 0.86 0.14 Positive values imply substituents are more hydrophobic than H Negative values imply substituents are less hydrophobic than H The value of is only valid for parent structures It is possible to calculate log P using  values Example: Cl Log P(theory) CONH2 meta-Chlorobenzamide Log P (observed) = log P(benzene) + Cl + CONH = 2.13 + 0.71 - 1.49 = 1.35 = 1.51 2 A QSAR equation may include both P and . P measures the importance of a molecule’s overall hydrophobicity (relevant to absorption, binding etc)  identifies specific regions of the molecule which might interact with hydrophobic regions in the binding site