3D QSAR Analysis of 6-Isoxazolinyl and Isoxazolidinyl Substituted Quinazolinones as Angiotensin-II Receptor Antagonists

Abstract

Semi-emperical AM1 calculation was performed on 6-isoxazolinyl and isoxazolidinyl substituted quinazolinones as A-II receptor antagonists. The best QSAR equation obtained from 19 analogs of training set molecules revealed statically significant equation with following stastics; coefficient of determination (r²) = 0.645525, cross validated value (q²) = 0.894626, standard error of estimate (s) = 0.117655, fisher's F-value = 3.434560. Further, robustness and predictivity of the model was assessed externally by r² predicted value (0.114659). This analysis revealed that steric, thermodynamic and electronic interactions are responsible for A-II receptor antagonistic activity. Based on QSAR results new analogues were designed and their IC₅₀ values were determined theoretically.