title: Synthesis and biological activity of modified peptide inhibitors of angiotensin-converting enzyme.
abstract: A series of non-sulfhydryl modified dipeptides related to CI-906, CI-907, and enalapril was prepared in which various isosteric moieties (O, S, SO, SO2) have been substituted for the amino group and in which the proline residue has been replaced with various hydrophobic amino acids. The compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme and in vivo for antihypertensive activity. Compound 7c, the most potent member of this series, had an in vitro IC50 of 1.4 X 10(-8) M and showed modest oral antihypertensive activity at 30 mg/kg in conscious, two kidney, one clip Goldblatt hypertensive rats. Structure-activity relationships are discussed.
authors.forename: W H
authors.initials: WH
authors.lastname: Roark
authors.forename: F J
authors.initials: FJ
authors.lastname: Tinney
authors.forename: D
authors.initials: D
authors.lastname: Cohen
authors.forename: A D
authors.initials: AD
authors.lastname: Essenburg
authors.forename: H R
authors.initials: HR
authors.lastname: Kaplan
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D004656:Enalapril; D006168:Guinea Pigs; D006977:Hypertension, Renal / Q000188:drug therapy; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D000077583:Quinapril; D051381:Rats; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007211:Indoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D004656:Enalapril; C038812:Indolapril; D000077583:Quinapril