Abstract

Essential structural and physicochemical requirement in terms of common pharmacophoric sites and secondary sites for inhibitory action of 5,6-diarylimidazo(2.1-b)thiazole have developed by the molecular modeling studies using an APEX-3D expert system. In addition to this 3 dimensional quantitative structure activity relationship equations have also been developed. Among several pharmacophoric models three models (1,2,3) having R2>0.84, chance<0.04, match>0.80, variables =<3 with four pharmacophoric sites in two models (1 and 2) and three pharmacophoric sites in model no.3, one secondary site in model 1 and two secondary sites in model 2 and three secondary sites in model 3 describe the variation in selective inhibition of cyclooxygenase-2 enzyme. To validate our models we have attempted to predict the activity of prediction set compounds, Model 3 was found the best-fit model. Total hydrophobicity (global property), H-acceptor (presence) at one of the oxygen atom of sulphonyl methyl positively contributes for the inhibitory activity suggesting that total hydrophobicity and electrostatic interactions are favorable for selective inhibition of cyclooxygenase-2 enzyme.