Synthesis of human renin inhibitory peptides, angiotensinogen transition-state analogs containing a retro-inverso amide bond

Chem Pharm Bull (Tokyo). 1990 Nov;38(11):3042-7. doi: 10.1248/cpb.38.3042.

Abstract

The experimental details for the synthesis of human renin inhibitors are described. In order to avoid 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 1a, which contained 2-(1-naphthylmethyl)-3-(N-phenethylcarbamoyl)propionyl residue (P4-P3) with a retro-inverso amide bond, L-histidine, and norstatine isoamylamide residue (P1-P1) as a transition-state mimic, had potent human renin inhibitory activity, and it lowered blood pressure when administered orally to common marmosets.

MeSH terms

  • Amides
  • Amino Acid Sequence
  • Angiotensinogen / analogs & derivatives*
  • Angiotensinogen / chemical synthesis
  • Angiotensinogen / chemistry
  • Angiotensinogen / pharmacology
  • Humans
  • Molecular Sequence Data
  • Renin / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Amides
  • Angiotensinogen
  • Renin