SYNTHESIS OF HUMAN RENIN INHIBITORY PEPTIDES, ANGIOTENSINOGEN TRANSITION-STATE ANALOGS CONTAINING A RETRO-INVERSO AMIDE BOND

The experimental details for the synthesis of human renin inhibitors are described. In order to aviod metabolic degradation of the Phe-His (P3-P2) amide bond in transition-state analogs, structurally modified acyl residues (P4-P3) were incorporated into the inhibitors. Compound la, which contained 2-(l-naphthylmethyl)-3-(N-phenethylcarba-moyl)propionyl residue (P4-P3) with a retro-inverso amide bond, L-histidine, and norstatine isoamylamide residue (Pi-P/) as a transition-state mimic, had potent human renin inhibitory activity, and it lowered blood pressure when administered orally to common marmosets. © 1990, The Pharmaceutical Society of Japan. All rights reserved.