Angiotensin converting enzyme inhibitors: N-substituted D-glutamic acid gamma dipeptides.
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 X 10(-9) M, respectively.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004151:Dipeptides / Q000494:pharmacology*; D005971:Glutamates / Q000138:chemical synthesis / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D005971:Glutamates; D007211:Indoles; C047231:1-(N-carbobenzoxy-gamma-glutamyl)indoline-2-carboxylic acid; C047232:1-(N-carbobenzoxy-gamma-glutamyl)perhydroindoline-2-carboxylic acid