Antihypertensive agents: angiotensin converting enzyme inhibitors. 1-[3-(Acylthio)-3-aroylpropionyl]-L-prolines.
A series of 1-[3-(acylthio)-3-aroylpropionyl]-L-proline derivatives was synthesized. A number of these compounds are potent angiotensin converting enzyme (ACE) inhibitors that lowered blood pressure in aorta-coarcted renal hypertensive rats. The most active derivatives are 1-[3(R)-(acetylthio) -3-substituted-benzoyl)-2(S)-methyl-propionyl]-L-prolines with an in vivo activity equivalent to SQ 14,225 (captopril). Structure-activity relationships are discussed. Changes in the configuration of the alpha-methyl group and the S-acetyl group affect the ACE activity. Coupling of 3-(substituted-benzoyl)-2-methylpropionic acids to L-proline via enol lactones is described.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D011759:Pyrrolidines; D011392:Proline