Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines.
The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.
Smith
E M
EM
Department of Medicinal Chemistry, Schering-Plough Corporation, Bloomfield, New Jersey 07003.
Swiss
G F
GF
Neustadt
B R
BR
Gold
E H
EH
Sommer
J A
JA
Brown
A D
AD
Chiu
P J
PJ
Moran
R
R
Sybertz
E J
EJ
Baum
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001920:Bradykinin / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D013438:Sulfhydryl Compounds; D011392:Proline; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin