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Generated: September 22, 2017

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Title: Phosphinylalkanoyl substituted prolines
Abstract:Esters of phosphinylalkanoyl prolines and phosphinylalkanoyl substituted prolines are inhibitors of angiotensin converting enzyme and are useful in the treatment of hypertension.
Inventor(s): Petrillo, Jr.; Edward W. (Pennington, NJ)
Assignee: E. R. Squibb & Sons, Inc. (Princeton, NJ)
Application Number:06/326,082
Patent Claims: 1. A compound having the formula ##STR27## or a non-toxic, physiologically acceptable salt thereof, wherein R.sub.1 is alkyl, aryl, arylalkyl, cycloalkyl, or cylcoalkylalkyl;

R.sub.2 and R.sub.4 each is independently hydrogen, alkyl or arylalkyl;

R.sub.3 is hydrogen or alkyl;

--R.sub.5 --COOR.sub.4 is ##STR28## R.sub.6 is cycloalkyl or aryl; R.sub.7 and R'.sub.7 together are --S--(CH.sub.2).sub.2 --S--; and

n is 0 or 1;

and wherein the term "aryl" refers to phenyl or phenyl substituted with halogen, alkyl, alkoxy, alkylthio, hydroxy, alkanoyl, nitro, amino, dialkylamino, or trifluoromethyl groups; the term "alkyl" refers to groups having 1 to 10 carbon atoms; the term "alkoxy" refers to groups having 1 to 8 carbon atoms; the term "cycloalkyl" refers to groups having 3 to 7 carbon atoms; and the term "alkanoyl" refers to groups having 2 to 9 carbon atoms.

2. A compound in accordance with claim 1 wherein n is 0.

3. A compound in accordance with claim 1 wherein each of R.sub.2 and R.sub.4 is hydrogen.

4. A compound in accordance with claim 1 wherein --R.sub.5 --COOR.sub.4 is ##STR29##

5. A compound in accordance with claim 1 wherein --R.sub.5 --COOR.sub.4 is ##STR30##

6. The compound in accordance with claim 1, (S)-7-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-1,4-dithia-7-azaspiro[4.4 ]nonane-8-carboxylic acid, or a physiologically acceptable salt thereof.

7. The compound in accordance with claim 1, (cis)-4-cyclohexyl-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline, or a physiologically acceptable salt thereof.

8. The compound in accordance with claim 1, (cis)-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-4-phenyl-L-proline, or a physiologically acceptable salt thereof.
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Fish and Richardson
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QuintilesIMS

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