3D-QSAR study on phenoxyalkylamine compounds of α1-adrenoceptor antagonist

The study of three-dimensional quantitative structure-activity relationship (3D-QSAR) of DDPH and its derivatives that have been known with their activity parameters has been developed using the comparative molecular field analysis (CoMFA) method. Here, (+)-DDPH crystal structure was selected as the active conformation model and comparisons between the influences of different charge calculation methods and grid setup were conducted. The coefficients of cross-validation (q2 ) and regression (r2 ) are 0.481 and 0.997, respectively. The standard error (SE) is 0.102. The research result suggests that the steric field makes more contributions to the activity than the electrostatic field. This model can help us not only in improving our understanding of the receptor-ligand interactions, but also in predicting the activity of derivatives and designing new compounds with better potency.