THEORETICAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS OF CONGENERIC AND NONCONGENERIC ALPHA(1)-ADRENOCEPTOR ANTAGONISTS - A CHEMOMETRIC STUDY

Molecular orbital calculations (AM1) and molecular modelling procedure s (QUANTA/CHARMm) have been performed both on a congeneric (prazosin a nalogs) and on a non-congeneric series of alpha(1)-adrenergic antagoni sts. A large variety of theoretical molecular descriptors has been obt ained and compared by principal component analysis (PCA). The generati ng optimal least squares estimations (GOLPE) procedure has been used t o derive quantitative structure-activity relationships (QSARs). Good p redictive QSAR models with a restricted pool of informative theoretica l descriptors have been obtained. These results support the generality of the theoretical QSAR approach proposed; in fact both congeneric an d non-congeneric molecular series were satisfactorily modeled. Moreove r, the high and well-defined physical information content encoded in t he theoretical descriptors considered allows the rationalization of th e structural heterogeneity of the molecules examined as differences in the complementary intermolecular interactions of the studied ligands towards their common receptor.