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EP0058427A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Substituted phosphonamides, a process for preparing the same and a pharmaceutical composition which is useful in the treatment of hypertension

Assignee: Merck and Co Inc
•
Filing: 1982-02-16
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Granted: —
•
Expires: 2002-02-16
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Abstract

Abstract There are disclosed substituted phosphonamides and related compounds of the general formula wherein: R, is alkyl or substituted alkyl of C 1 -C 6 wherein the substituent is halo, amino, acylamino; aralkyl wherein the alkyl is C 1 -C 4 optionally substituted by amino or acylamino and wherein the aryl function is phenyl or naphthyl optionally substituted by halo or hydroxyl; or, heteroaralkyl wherein the alkyl is C 1 -C 4 optionally substituted by amino or acylamino and wherein the heteroaryl group can be indolyl or thienyl; R 2 is H, lower alkyl of C 1 -C 4 , aralkyl. R 3 is lower alkyl of C 1 -C 6 optionally substituted by an amino group; R 4 is H, lower alkyl of C 1 -C 6 , aralkyl. X is (CH 2 ) n wherein n is 1 or 2, CH-OCH 3 , CH-OH, or S; and, the pharmaceutically acceptable salts thereof. THese compounds are useful as converting enzyme inhibitors and as antihypertensives.

Inventors

  • 👤 William J. Greenlee
  • 👤 Arthur A. Patchett
  • 👤 Elbert E. Harris
  • 👤 Eugene D. Thorsett

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-06 02:39
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06191; C07F; C07F9/00; C07F9/02; C07F9/547; C07F9/553; C07F9/572; C07F9/6536; C07F9/6539; A; A61; A61K; A61K38/00

Claims Analysis

Total Claims: 3
Claim 1
Independent Claim 221 words
A process for preparing a substituted phosphonamide of the general formula wherein: R 1 is alkyl or substituted alkyl of C 1 -C 6 wherein the substituent is halo, amino, acylamino; aralkyl wherein the alkyl is C l -C 4 optionally substituted by amino or acylamino and wherein the aryl function is phenyl or naphthyl optionally substituted by halo or hydroxyl; or, heteroaralkyl wherein the alkyl is C 1 -C 4 optionally substituted by amino or acylamino and wherein the heteroaryl group can be indolyl or thienyl; R 2 is H, lower alkyl of C 1 -C 4 , aralkyl- R 3 is lower alkyl of C 1 -C 6 optionally substituted by an amino group; R 4 is H, lower alkyl of C 1 -C 6 , aralkyl X is (CH 2 ) n wherein n is 1 or 2, CH-OCH 3 , CH-OH, or S; and, the pharmaceutically acceptable salts thereof comprising: a) converting a phosphonic acid diester to its monoester chloride in the presence of phosphorous pentachloride in an inert solvent; b) reacting said monoester with a dipeptide derivative in the presence of a base in an inert solvent; c) recovering therefrom said substituted phosphonamide compound; and,. d) if desired, removing benzyloxy protecting groups by either hydrogenolysis and/or saponification to produce the acid, diacid or monoester analogs thereof.
Claim 2
Dependent Claim 221 words
A process for preparing a substituted phosphonamide of the general formula wherein: R 1 is alkyl or substituted alkyl of C 1 -C 6 wherein the substituent is halo, amino, acylamino; aralkyl wherein the alkyl is C l -C 4 optionally substituted by amino or acylamino and wherein the aryl function is phenyl or naphthyl optionally substituted by halo or hydroxyl; or, heteroaralkyl wherein the alkyl is C 1 -C 4 optionally substituted by amino or acylamino and wherein the heteroaryl group can be indolyl or thienyl; R 2 is H, lower alkyl of C 1 -C 4 , aralkyl- R 3 is lower alkyl of C 1 -C 6 optionally substituted by an amino group; R 4 is H, lower alkyl of C 1 -C 6 , aralkyl X is (CH 2 ) n wherein n is 1 or 2, CH-OCH 3 , CH-OH, or S; and, the pharmaceutically acceptable salts thereof comprising: a) converting a phosphonic acid diester to its monoester chloride in the presence of phosphorous pentachloride in an inert solvent; b) reacting said monoester with a dipeptide derivative in the presence of a base in an inert solvent; c) recovering therefrom said substituted phosphonamide compound; and,. d) if desired, removing benzyloxy protecting groups by either hydrogenolysis and/or saponification to produce the acid, diacid or monoester analogs thereof.
Claim 3
Dependent Claim 27 words
The process of Claim 1 wherein said dipeptide derivative is coupled directly to a phosphonyl dichloride to obtain said substituted phosphonamide compound as its diacid or monoester.

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