75776-51-1Relevant articles and documents
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines
Krapcho,Turk,Cushman,Powell,DeForrest,Spitzmiller,Karanewsky,Duggan,Rovnvak,Schwartz,Natarajan,Godfrey,Ryono,Neubeck,Atwa,Petrillo Jr.
, p. 1148 - 1160 (2007/10/02)
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.
CARBOXYALKANOYL AND HYDROXYCARBAMOYLALKANOYL DERIVATIVES OF SUBSTITUTED PROLINES
-
, (2008/06/13)
Compounds, compositions and method of alleviating hypertension using a compound of the formula STR1 wherein R is hydrogen or lower alkyl;R 1 is hydrogen, lower alkyl or phenyl-lower alkyl; R 2 is hydrogen, lower alkyl or phenyl lower alkyl or halo substituted lower alkyl;R 3 is hydroxy,--NHOH or lower alkoxy; Pr-COOR is a substituted proline of the structures STR2 R 4 is halogen, keto, azido, cycloalkyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, STR3 or Y--R 6 ; R 5 is hydrogen or lower alkyl;Y is oxygen or sulfur; R 6 is lower alkyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, 1-or 2-naphthyl, substituted 1-or 2-naphthyl, biphenyl, or substituted biphenyl; R. sub.7 is halogen or--Y--R. sub.8 ;R 8 is lower alkyl, phenyl, phenyl-lower alkyl substituted phenyl-lower alkyl, biphenyl, napthyl, or the R 8 groups join to complete an unsubstituted 5-or 6-membered ring or such ring wherein one or more carbon atoms are substituted by a lower alkyl or di(lower alkyl) group; R 9 is keto, phenyl, 2-or 4-hydroxyphenyl;n is 0 or 1; and salts thereof.
