Quantitative structure-activity relationships of alpha(1) adrenergic antagonists

Abstract

A quantitative structure-activity relationship study with respect to selectivity for alpha(1) adrenoreceptor subtypes (alpha(1a), alpha(1b) and alpha(1d)) of a wide series of structurally heterogeneous alpha(1) adrenoreceptor antagonists has been performed. A large variety of molecular descriptors have been calculated and then analyzed by a heuristic method. The orthogonalization of the descriptors has been applied to build the QSAR equations. Ad hoc defined shape descriptors calculated by the Connolly algorithm with respect to reference supermolecules have also been considered in the rationalization of the mechanism of the activity of the ligands acting as antagonists on all three subtypes of alpha(1) adrenoreceptors.