75776-55-5

Upstream product

• 64187-47-9 1-benzyloxycarbonyl-4-keto-L-proline 
• 149-73-5 trimethyl orthoformate 

Relevant academic research and scientific papers

Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines

Analogues of captopril, enalaprilat, and the phosphinic acid [[hydroxy(4-phenylbutyl)phosphinyl]acetyl)-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.

DERIVATIVES OF MERCAPTOACYL PROLINES AND PIPECOLIC ACIDS

This invention is directed to compounds of the formula STR1 and various intermediates therefore. The final products possess useful hypotensive activity.

MERCAPTOACYL DERIVATIVES OF KETO SUBSTITUTED PROLINE AND PIPECOLIC ACID

This invention is directed to compounds of the formula STR1 which are useful in the treatment of hypertension.