REFINEMENT OF A MOLECULAR-MODEL OF ANGIOTENSIN-II (AII) EMPLOYED IN THE DISCOVERY OF POTENT NONPEPTIDE ANTAGONISTS

A novel conformational model of AII, Model II, had been employed previ ously in the design of potent benzylimidazole AII antagonists (J. Med. Chem. 1991, 34,1514-1517). This paper considers this model in relatio n to the recently described potent AII analogs [hCys3,5]-AII, and [Sar 1,hCys3,5,IIe8]-AII. Conformational analysis of Ac-S,S-cyclo(hCys-Ala- hCys)-NH2 suggests a family of modified conformations for AII, Model I II, which retains the topological arrangement of functional groups in Model II that had been employed in nonpeptide analog design.