2-D AND 3-D MODELING OF IMIDAZOLINE RECEPTOR LIGANDS - INSIGHTS INTO PHARMACOPHORE

A 3-D quantitative structure-activity relationship (3-D QSAR) study wa s carried out using comparative molecular field analysis (CoMFA) on bo th imidazoline (I2R) and alpha(2) receptor binding affinities of a lar ge series of 2-substituted imidazolines. Significant cross-validated c orrelations, having promising predictive ability, were obtained along with 3-D pharmacophore models that defined the spatial regions where s teric and electrostatic interactions may modulate the in vitro binding affinities and indicated possible physicochemical and structural requ irements for I-2/alpha(2) receptor selectivity. (C) 1997 Elsevier Scie nce Ltd.