1. Antihypertensive agents: angiotensin converting enzyme inhibitors. 1-[3-(Acylthio)-3-aroylpropionyl]-L-prolines
- Author
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J. D. Albright, F. J. Mcevoy, and F. M. Lai
- Subjects
Magnetic Resonance Spectroscopy ,Pyrrolidines ,Proline ,Stereochemistry ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,Structure-Activity Relationship ,chemistry.chemical_compound ,X-Ray Diffraction ,In vivo ,Drug Discovery ,medicine ,Animals ,Structure–activity relationship ,Ace activity ,Antihypertensive Agents ,biology ,Angiotensin-converting enzyme ,Captopril ,Nuclear magnetic resonance spectroscopy ,Enol ,Rats ,Blood pressure ,chemistry ,biology.protein ,Molecular Medicine ,Rabbits ,medicine.drug - Abstract
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.
- Published
- 1983
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