title: Angiotensin-converting enzyme inhibitors: synthesis and structure-activity relationships of potent N-benzyloxycarbonyl tripeptide inhibitors.
abstract: A new series of gamma-D-Glu-containing N-benzyloxycarbonyl (Z) tripeptide inhibitors of angiotensin-converting enzyme (ACE) was synthesized. The effect of varying the antepenultimate amino acid residue in this series on the biological activity was studied. Introduction of Lys and Orn residues at the P1 position provided the most potent inhibitors, 25a and 25b (IC50: 3.5 and 4.9 x 10(-9) M, respectively), which exhibited an oral antihypertensive activity. This result suggests that basic amino acid residues at the P1 position play an important role in binding with the S1 subsite of ACE in this series. Oral antihypertensive activity of selected compounds was evaluated.
authors.forename: T
authors.initials: T
authors.lastname: Sawayama
authors.forename: M
authors.initials: M
authors.lastname: Tsukamoto
authors.forename: T
authors.initials: T
authors.lastname: Sasagawa
authors.forename: K
authors.initials: K
authors.lastname: Nishimura
authors.forename: R
authors.initials: R
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Deguchi
authors.forename: K
authors.initials: K
authors.lastname: Takeyama
authors.forename: K
authors.initials: K
authors.lastname: Hosoki
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007211:Indoles; C062358:1-(N(2)-benzyloxycarbonyllysyl-gamma-glutamyl)octahydro-1H-indole-2-carboxylic acid; C062359:1-(N(2)-benzyloxycarbonylornithyl-gamma-glutamyl)octahydro-1H-indole-2-carboxylic acid