Inhibitors of bacterial collagenase

Claim 1

A method for inhibiting bacterial collagenase in vivo wherein the bacteria are selected from the group consisting of Clostridium and Pseudomonas, which comprises administering to a human being a collagenase inhibiting effective amount of a pharmaceutical composition including a compound of the formula: ##STR12## wherein R is alkyl, aralkyl, aryl, alkoxy, aryloxy, hydroxy or pharamceutically acceptable salts thereof; R 1 is hydrogen, alkali metal, lower alkyl, phenyl lower alkyl, or phenyl, or substituted phenyl wherein the substituent is halo, lower alkoxy or lower alkyl or nitro or carboxy or cyano, and pharmaceutically acceptable salts thereof; R 2 , R 3 and R 4 are hydrogen or alkyl; R 2 and R 4 are selected from the group consisting of straight and branched chain alkyl, hydroxy alkyl, carboxy alkyl, aralkyl, amino alkyl, carboxamide alkyl, mercapto alkyl, phenyl alkyl, hydroxy phenyl alkyl, guanidino alkyl, imidazoyl alkyl, indolyl alkyl, and pyrrolidinyl; R 3 and R 4 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; Y is alkoxy, aryloxy, primary amide, alanine benzyl ester or ##STR13## where R 5 and R 6 is hydrogen or alkyl; R 5 and R 6 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; and X is hydroxyl or pharmaceutically acceptable salts thereof, in admixture with a pharmaceutically acceptable carrier.

Claim 2

A method for inhibiting bacterial collagenase in vivo wherein the bacteria are selected from the group consisting of Clostridium and Pseudomonas, which comprises administering to a human being a collagenase inhibiting effective amount of a pharmaceutical composition including a compound of the formula: ##STR12## wherein R is alkyl, aralkyl, aryl, alkoxy, aryloxy, hydroxy or pharamceutically acceptable salts thereof; R 1 is hydrogen, alkali metal, lower alkyl, phenyl lower alkyl, or phenyl, or substituted phenyl wherein the substituent is halo, lower alkoxy or lower alkyl or nitro or carboxy or cyano, and pharmaceutically acceptable salts thereof; R 2 , R 3 and R 4 are hydrogen or alkyl; R 2 and R 4 are selected from the group consisting of straight and branched chain alkyl, hydroxy alkyl, carboxy alkyl, aralkyl, amino alkyl, carboxamide alkyl, mercapto alkyl, phenyl alkyl, hydroxy phenyl alkyl, guanidino alkyl, imidazoyl alkyl, indolyl alkyl, and pyrrolidinyl; R 3 and R 4 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; Y is alkoxy, aryloxy, primary amide, alanine benzyl ester or ##STR13## where R 5 and R 6 is hydrogen or alkyl; R 5 and R 6 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; and X is hydroxyl or pharmaceutically acceptable salts thereof, in admixture with a pharmaceutically acceptable carrier.

Claim 7

A method of inhibiting the action of a bacterial collagenase in vitro wherein the bacteria are selected from the group consisting of clostridium and Pseudomonas, by allowing the collagenase to react with an inhibition-effective amount of a compound of the formula: ##STR14## wherein R is alkyl, aralkyl, aryl, alkoxy, aryloxy, hydroxy or pharmaceutically acceptable salts thereof; R 1 is hydrogen, alkali metal, lower alkyl, phenyl lower alkyl, or phenyl, or substituted phenyl wherein the substituent is halo, lower alkoxy or lower alkyl or nitro or carboxy or cyano, and pharmaceutically acceptable salts thereof; R 2 , R 3 and R 4 are hydrogen or alkyl; R 2 and R 4 are selected from the group consisting of straight and branched chain alkyl, hydroxy alkyl, carboxy alkyl, aralkyl, amino alkyl, carboxamide alkyl, mercapto alkyl, phenyl alkyl, hydroxy phenyl alkyl, guanidino alkyl, imidazoyl alkyl, indolyl alkyl, and pyrrolidinyl; R 3 and R 4 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; Y is alkoxy, aryloxy, primary amide, alanine benzyl ester or ##STR15## where R 5 and R 6 is hydrogen or alkyl; R 5 and R 6 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; and X is hydroxyl or pharmaceutically acceptable salts thereof, in admixture with a pharmaceutically acceptable carrier in an appropriate solution.

Claim 8

A method of inhibiting the action of a bacterial collagenase in vitro wherein the bacteria are selected from the group consisting of clostridium and Pseudomonas, by allowing the collagenase to react with an inhibition-effective amount of a compound of the formula: ##STR14## wherein R is alkyl, aralkyl, aryl, alkoxy, aryloxy, hydroxy or pharmaceutically acceptable salts thereof; R 1 is hydrogen, alkali metal, lower alkyl, phenyl lower alkyl, or phenyl, or substituted phenyl wherein the substituent is halo, lower alkoxy or lower alkyl or nitro or carboxy or cyano, and pharmaceutically acceptable salts thereof; R 2 , R 3 and R 4 are hydrogen or alkyl; R 2 and R 4 are selected from the group consisting of straight and branched chain alkyl, hydroxy alkyl, carboxy alkyl, aralkyl, amino alkyl, carboxamide alkyl, mercapto alkyl, phenyl alkyl, hydroxy phenyl alkyl, guanidino alkyl, imidazoyl alkyl, indolyl alkyl, and pyrrolidinyl; R 3 and R 4 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; Y is alkoxy, aryloxy, primary amide, alanine benzyl ester or ##STR15## where R 5 and R 6 is hydrogen or alkyl; R 5 and R 6 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms; and X is hydroxyl or pharmaceutically acceptable salts thereof, in admixture with a pharmaceutically acceptable carrier in an appropriate solution.