Synthesis and structure-activity relationships of potent new angiotensin converting enzyme inhibitors containing saturated bicyclic amino acids.
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.
D000596:Amino Acids / Q000138:chemical synthesis / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors