US4818749A
Expired / Lapsed
US
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Carboxyalkyl dipeptides and medical use thereof in treating hypertension and congestive heart failure
Assignee: Merck Sharp & Dohme LLC
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Filing: 1987-11-04
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Granted: 1989-04-04
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Expires: 2007-11-04
Abstract
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 <IMAGE> I and <IMAGE> II and the pharmaceutically acceptable salts thereof, wherein R and R6 are the same or different and are hydroxy or lower alkoxy; R1 is benzyloxylower alkyl or benzylthiolower alkyl; R2 is benzylthiomethyl, 2-phyenylethylthiomethyl, napthylmethylthiomethyl, methylbenzylthiomethyl, 2-(carboxyphenyl)ethyl or 2-(alkoxycarbonylphenyl)ethyl) and R3 is hydrogen, lower alkyl or aminolower alkyl.
Inventors
- 👤 Elijah H. Gold
- 👤 Bernard R. Neustadt
- 👤 Elizabeth M. Smith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 00:51
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/02; C07K5/022; C07K5/0222; A; A61; A61P; A61P43/00; A61P9/00; A61P9/12; A61K; A61K38/00
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
49 words
A compound represented by the formula ##STR12## and the pharmaceutically acceptable salts thereof, wherein R and R 6 are the same or different and are hydroxy or lower alkoxy; R 2 is benzylthiomethyl, 2-phenylethylthiomethyl, naphthylmethylthiomethyl, methylbenzylthiomethyl, carboxyphenylethyl or alkoxycarbonylphenylethyl; and R 3 is hydrogen, lower alkyl or aminolower alkyl.
Claim 2
Dependent Claim
49 words
A compound represented by the formula ##STR12## and the pharmaceutically acceptable salts thereof, wherein R and R 6 are the same or different and are hydroxy or lower alkoxy; R 2 is benzylthiomethyl, 2-phenylethylthiomethyl, naphthylmethylthiomethyl, methylbenzylthiomethyl, carboxyphenylethyl or alkoxycarbonylphenylethyl; and R 3 is hydrogen, lower alkyl or aminolower alkyl.
Claim 3
Dependent Claim
10 words
A compound of claim 1 wherein R is lower alkoxy.
Claim 4
Dependent Claim
9 words
A compound of claim 1 wherein R is ethoxy.
Claim 5
Dependent Claim
10 words
A compound of claim 1 wherein R 6 is hydroxy.
Claim 6
Dependent Claim
11 words
A compound of claim 1 wherein R 3 is lower alkyl.
Claim 7
Dependent Claim
10 words
A compound of claim 1 wherein R 3 is methyl.
Claim 8
Dependent Claim
10 words
A compound of claim 1 wherein R 2 is benzylthiomethyl.
Claim 9
Dependent Claim
10 words
A compound of claim 1 wherein R 2 is 2-phenylethylthiomethyl.
Claim 10
Dependent Claim
10 words
A compound of claim 1 wherein R 2 is naphthylmethylthiomethyl.
Claim 11
Dependent Claim
10 words
A compound of claim 1 wherein R 2 is methylbenzylthiomethyl.
Claim 12
Dependent Claim
10 words
A compound of claim 1 wherein R 2 is carboxyphenylethyl.
Claim 13
Dependent Claim
10 words
A compound of claim 1 wherein R 2 is alkoxycarbonylphenylethyl.
Claim 14
Dependent Claim
10 words
A compound of claim 12 wherein R 2 is ethoxycarbonylphenylethyl.
Claim 15
Dependent Claim
30 words
A compound of claim 1 wherein R is lower alkoxy, R 6 is hydroxy, R 3 is lower alkyl, and R 2 is benzylthiomethyl, 2-phenylethylthiomethyl, naphthylmethylthiomethyl, methylbenzylthiomethyl, carboxyphenylethyl or ethoxycarbonylphenylethyl.
Claim 16
Dependent Claim
14 words
A compound of claim 14 wherein R is ethoxy and R 3 is methyl.
Claim 17
Dependent Claim
17 words
A compound of claim 14 selected from 1-[N-[1(R)-ethoxycarbonyl-2-(4-methylbenzylthio)ethyl]-(R,S)-alanyl]-cis,syn-perhydroindole-2(S)-carboxylic acid; 1-[N-[1(S)-ethoxycarbonyl-3-(4-ethoxycarbonylphenyl)propyl]-(S)-alanyl]-cis,syn-perhydroindole-2(S)carboxylic acid; 1-[N-[1(R)-ethoxycarbonyl-2-(benzylthio)ethyl]-(R,S)-alanyl]-cis,syn-perhydroindole-2(S)-carboxylic acid; 1-[N-[1(R)-ethoxycarbonyl-2-(phenylthio)ethyl]-(S)-alanyl]-cis,syn-perhydroindole-2(S)-carboxylic acid; 1-[N-[1(R)-ethoxycarbonyl-2-(2-naphthylmethylthio)ethyl]-(S)-alanyl]-cis,syn-perhydroindole-2(S)-carboxylic acid.
Claim 18
Dependent Claim
14 words
A compound of claim 11 wherein R is hydroxy and R 3 is methyl.
Claim 19
Dependent Claim
9 words
A compound of claim 17 which is 1-[N-(1(S)-carboxy-3-(4-carboxyphenyl)propyl]-(S)-alanyl]-cis,syn-perhydroindole-2(S)-carboxylic acid.
Claim 20
Dependent Claim
21 words
An antihypertensive pharmaceutical composition comprising an antihypertensive effective amount of a compound of claim 1, together with a pharmaceutically acceptable carrier.
Claim 21
Dependent Claim
22 words
A method for reducing blood pressure in a hypertensive mammal which comprises administering to such a mammal a composition of claim 19.
Claim 22
Dependent Claim
35 words
A method of treating congestive heart failure in a mammal in need of such treatment comprising administering to such a mammal an amount of a compound of claim 1 effective in treating congestive heart failure.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-04-03 | 1992-10-03 | 1993-04-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-04-03 | 1996-10-03 | 1997-04-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-04-03 | 2000-10-03 | 2001-04-04 | $7700.00 | Window Closed / Lapsed |