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.
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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