Angiotensin converting enzyme inhibitors: structure-activity profile of 1-benzazepin-2-one derivatives.
The preparation of a series of 3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-1-acetic acid derivatives 5a-y by reductive amination of 2,3,4,5-tetrahydro-1H-1-benzazepine-2,3-dione (7) with L-amino acid derivatives is described. The compounds were tested for inhibition of angiotensin converting enzyme. The structure-activity profile of the series is discussed. Compound 5a was especially potent when tested in dogs for inhibition of angiotensin I pressor response, having an ID50 = 0.07 mg/kg po.
D000596:Amino Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D006973:Hypertension / Q000188:drug therapy; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines