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|Title:||Carboxyalkyl dipeptides and anti-hypertensive use thereof|
|Abstract:||The present invention relates to carboxyalkyl dipeptides which are inhibitors of angiotensin-converting enzyme and are useful as antihypertensive agents and in the treatment of congestive heart failure. The compounds of the present invention are compounds of the formulae ##STR1## and the pharmaceutically acceptable salts thereof, wherein R and R.sup.6 are the same or different and are hydroxy or lower alkoxy; R.sup.1 is benzyloxylower alkyl or benzylthiolower alkyl; R.sup.2 is benzylthiomethyl, 2-phenylethylthiomethyl, naphthylmethylthiomethyl, methylbenzylthiomethyl; 2-(carboxyphenyl)ethyl or 2-(alkoxycarbonylphenyl)ethyl; and R.sup.3 is hydrogen, lower alkyl or aminolower alkyl.|
|Inventor(s):||Gold; Elijah H. (West Orange, NJ), Neustadt; Bernard R. (West Orange, NJ), Smith; Elizabeth M. (Verona, NJ)|
|Assignee:||Schering Corporation (Kenilworth, NJ)|
|Filing Date:||Mar 23, 1987|
|Claims:||1. A compound represented by the formula ##STR12## and the pharmaceutically acceptable salts thereof, wherein R and R.sup.6 are the same or different and are hydroxy or lower alkoxy; |
R.sup.1 is benzyloxylower alkyl or benzylthiolower alkyl; and
R.sup.3 is hydrogen, lower alkyl or aminolower alkyl.
2. A compound of claim 1 wherein R is lower alkoxy.
3. A compound of claim 1 wherein R is ethoxy.
4. A compound of claim 1 wherein R.sup.6 is hydroxy.
5. A compound of claim 1 wherein R.sup.3 is lower alkyl.
6. A compound of claim 1 wherein R.sup.3 is methyl.
7. A compound of claim 1 wherein R.sup.1 is benzyloxymethyl.
8. A compound of claim 1 wherein R.sup.1 is benzylthiomethyl.
9. A compound of claim 1 wherein R is lower alkoxy, R.sup.6 is hydroxy, R.sup.3 is lower alkyl, and R.sup.1 is benzyloxymethyl or benzylthiomethyl.
10. A compound of claim 9 wherein R is ethoxy and R.sup.3 is methyl.
11. A compound of claim 10 which is N-(1(R)-ethoxycarbonyl-2-benzylthioethyl)-(R,S)-alanyl-(S)-proline.
12. A compound of claim 10 which is N-(1(S)-ethoxycarbonyl-2-benzyloxyethyl)-R,S)-alanyl-(S)-proline.
13. An antihypertensive pharmaceutical composition comprising an antihypertensive effective amount of a compound of claim 1, together with a phartmaceutically acceptable carrier.
14. A method for reducing blood pressure in a hypertensive mammal which comprises administering to such a mammal a composition of claim 13.
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