Synthesis and structure-activity relationships of potent new angiotensin converting enzyme inhibitors containing saturated bicyclic amino acids

J Med Chem. 1987 Jun;30(6):992-8. doi: 10.1021/jm00389a006.

Abstract

The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfhydryl and non-sulfhydryl ACE inhibitors to give compounds equipotent to captopril and enalapril both in vitro and in vivo. Structure-activity relationships are discussed. Compound 11a (CI-907, indolapril) has advanced to clinical evaluation.

MeSH terms

  • Amino Acids / chemical synthesis
  • Amino Acids / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors*
  • Animals
  • Blood Pressure / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Male
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Angiotensin-Converting Enzyme Inhibitors
  • Enzyme Inhibitors