Classical QSAR Modeling of CCR5 Receptor Binding Affinity of Substituted Benzylpyrazoles

Abstract

CCR5 receptor binding affinity of a series of substituted benzylpyrazole derivatives was subjected to QSAR study using Fujita-Ban type analysis and a mixed approach based on Hansch and Fujita-Ban analyses. Apart from appropriate indicator variables encoding different group contributions, different physicochemical variables like hydrophobicity (π), electronic (Hammett σ) and steric (molar refractivity, STERIMOL values) parameters of phenyl ring substituents of the benzyl moiety of the compounds were used as predictor variables. Additionally, Wang-Ford charges of the common atoms of the compounds calculated from molecular electrostatic potential surface of AM1 optimized geometries of the compounds and various topological parameters were used as additional descriptors. The variables for the multiple regression analyses were selected based on principal component factor analysis and generated equations were statistically validated using leave-one-out technique and predicting the binding affinities of test set compounds. The analysis explores the substitutional requirements of the phenyl nucleus of the benzylpyrazole moiety of the compounds for effective binding with CCR5 receptor.