Design and synthesis of alpha,beta-unsaturated carbonyl compounds as potential ACE inhibitors.
The alpha,beta-unsaturated amide that is incorporated into the basic structural frame of a simple substrate molecule of angiotensin converting enzyme was found to serve as a Michael acceptor for the catalytic carboxylate of Glu-127, inhibiting the enzyme irreversibly.
Park Choo
H Y
HY
School of Pharmacy, Ewha Womans University, 120-750, Seoul, South Korea. hypark@mm.ewha.ac.kr
Peak
K H
KH
Park
J
J
Kim
D H
DH
Chung
H S
HS
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; C412577:N-(2-(3-phenyl-2-propenoylamino)propanoyl)proline; D011392:Proline; D007703:Peptidyl-Dipeptidase A