Quantitative structure-activity relationships of alpha1 adrenergic antagonists.

A quantitative structure-activity relationship study with respect to selectivity for alpha1 adrenoreceptor subtypes (alpha1a, alpha1b and alpha1d) of a wide series of structurally heterogeneous alpha1 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 alpha1 adrenoreceptors.