CoMFA study on selective human β3-adrenoceptor agonists

Abstract

Comparative molecular field analysis (CoMFA) was performed on a series of 47 compounds as potent selective human β3-adrenoceptor (AR) agonists. Low energy conformation of the most active compound in the chosen series was found by Molecular dynamics simulated annealing method. The statistically significant model was established from 33 molecules, which were validated by evaluation of test set of 14 compounds. The fit atom based alignment yielded best predictive CoMFA model (r2 cv=0.583, r2 cnv=0.992, F Value=534.974, SEE=0.074, r2 pred=0.743 with six components). The contour maps obtained from 3D-QSAR studies were appraised for the activity trends of the molecules analyzed. The results indicate that the steric, electrostatic substituents play significant role in β3-AR activity and potency of these compounds. The data generated from the present study can be used as putative pharmacophore in the design of novel, potent, human β3-adrenoceptor agonists as anti-obesity and anti-diabetic agents.