CoMFA methodology in structure-activity analysis of hexahydro- and octahydropyrido[1,2- c]pyrimidine derivatives based on affinity towards 5-HT 1A, 5-HT 2A and α 1-adrenergic receptors

Abstract

Structural features of the pyrido[1,2- c]pyrimidine derivatives with arylpiperazine moiety and their affinities towards 5-HT 1A, 5-HT 2A and α 1-adrenergic receptors were analyzed using the CoMFA procedure. On the basis of 3D-QSAR models for the 5-HT 2A and α 1-adrenergic receptors, four compounds with expected better affinity/selectivity were proposed and synthesized. The affinities obtained confirm experimentally the usefulness of CoMFA models. Our results suggest that active conformations adopted by the studied molecules when interacting with the receptors are neutral instead of the protonated ones.