Angiotensin converting enzyme inhibitors: N-substituted D-glutamic acid .gamma.-dipeptides

Abstract
The preparation of two series of N-carbobenzoxy-.gamma.-D-glutamyl secondary 2S amino acids and (N-substituted .gamma.-D-glutamyl)indoline-2(S)-carboxylic acid dipeptides is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound, and the structure-activity relationship is discussed. Oral and iv inhibition of AI pressor response in vivo of selected compounds in Table II is also discussed. The most potent compounds in vitro, 3 and 6a, had an ACE IC50 of 7 and 2.7 .times. 10-9 M, respectively.