DERIVATION OF A 3D PHARMACOPHORE MODEL FOR THE ANGIOTENSIN-II SITE ONE RECEPTOR

A systematic search has been used to derive a hypothesis for the recep tor-bound conformation of A-II antagonists at the AT(1) receptor. The validity of the pharmacophore hypothesis has been tested using CoMFA, which included 50 diverse A-II antagonists, spanning four orders of ma gnitude in activity. The resulting cross-validated R(2) of 0.64 (conve ntional R(2) of 0.76) is indicative of a good predictive model of acti vity, and has been used to estimate potency for a variety of non-pepti dyl antagonists. The structural model for the non-peptide has been com pared with respect to the natural substrate, A-II, by generating pepti de to non-peptide overlays.