Synthesis and pharmacology of the potent angiotensin-converting enzyme inhibitor N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanyl-(S)-pyroglutamic acid.
Structure 3a, a potent angiotensin-converting enzyme inhibitor, was prepared in five steps from L-(+)-alpha-amino-4-phenylbutyric acid by construction of the activated side-chain ester 16, displacement with L-pyroglutamate ester anion, and deblocking. Diastereomer separation was accomplished by chromatography at the diester stage, 17. Pharmacological assays established that 3a parallels enalapril in its ability to inhibit converting enzyme and lower blood pressure.
D000758:Anesthesia; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004039:Diet, Sodium-Restricted; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D004656:Enalapril / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy; D006978:Hypertension, Renovascular / Q000188:drug therapy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; C047230:N-(1-(ethoxycarbonyl)-3-phenylpropyl)-alanyl-pyroglutamic acid; D002216:Captopril