title: Angiotensin-converting enzyme inhibitors. 2. Perhydroazepin-2-one derivatives.
abstract: alpha-[(3S)-3-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2-oxo-6 or 7-phenylperhydroazepin-1-yl]acetic acids (monoester monoacids) and their dicarboxylic acids were synthesized, and their angiotensin-converting enzyme (ACE) inhibitory activities were evaluated. The dicarboxylic acids having phenyl substituents at the 6R, 6S, and 7S positions on the azepinone ring showed potent inhibition in vitro. The corresponding monoester monoacids, when administered orally, suppressed the pressor response to angiotensin I administered intravenously. The monoester monoacids having the phenyl substituent at the 6-position showed a longer duration of action than one having the substituent at the 7-position. The structure-activity relationship was studied on the basis of the conformational energy calculation.
authors.affiliation: Chemical Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yanagisawa
authors.forename: S
authors.initials: S
authors.lastname: Ishihara
authors.forename: A
authors.initials: A
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Kanazaki
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Koike
authors.forename: Y
authors.initials: Y
authors.lastname: Iijima
authors.forename: K
authors.initials: K
authors.lastname: Oizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Hata
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D008968:Molecular Conformation; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001381:Azepines; C048618:hexahydroazepine