Small organic molecules that increase the activity of gelatinase a in ocular cells

A pharmaceutically acceptable composition comprising:

• one or more compounds selected from the following formula:
• wherein W is selected from the group consisting of oxygen and sulfur;
• Z is selected from the group consisting of oxygen and sulfur;
• R1 is a substituted or unsubstituted C6-25 aryl
• wherein, when R1 is substituted, R1 is substituted with one or more substituents selected from the group consisting of C1-25 alkyl, C1-25 alkenyl, C1-25 alkynyl, C1-25 alkoxyl, C1-25 alkenoxy, hydroxy, carboxy, amino, C1-25 (N-alkylcarbonyl)amino, C1-25 (N-alkylcarbonyl)-N-alkylamino, C1-25 (N-alkylcarbonylalkyl)amino, cyano, nitro, sulfo, sulfino, sulfhydryl, halo, C1-25 haloalkyl, trifluoromethyl, C1-25 trifluoromethylalkyl, C6-30 arylalkyl, C6-30 aryl, C1-25 N-alkylamino, C1-25 N-dialkylamino, C1-25 (N-alkyl-N-alkenyl)amino, C1-25 N-dialkenylamino, C1-25 alkylsulfonyl, C1-25 alkylsulfinyl, C1-25 alkylthio, hydrido, C1-25 cyanoalkyl, C1-25 acyl, C1-25 alkylcarbonyloxy, nitroso, C1-25 alkoxyalkyl, C1-25 alkoxycarbonyl, C1-25 hydroxyalkyl, thiocarboxy, C1-25 thiocarboxyalkyl, C1-25 alkylthiocarbonyl, C1-25 alkylthiocarbonylalkyl, C1-25 alkoxythiocarbonyl, C1-25 alkoxythiocarbonylalkyl, sulfamoyl, sulfinamoyl, C1-25 N-alkylsulfamoyl, C1-25 N-dialkylsulfamoyl, C1-25 N-alkylsulfinamoyl, C1-25 N-dialkylsulfinamoyl, C1-25 sulfamoylalkyl, C1-25 sulfinamoylalkyl, aminocarbonyl, C1-25 aminocarbonylalkyl aminocarbonylmethyl, C1-25 N-alkylaminocarbonyl, C1-25 N-dialkylaminocarbonyl, C1-25 alkoxycarbonylamino, thiocarbamoyl, C1-25 thiocarbamoylalkyl, C1-25 (N-alkyl)thiocarbamoyl, C1-25 (N-dialkyl)thiocarbamoyl, aminothio, C1-25 alkylaminothio, C1-25 N-dialkylaminothio, C1-25 cycloalkyl, C1-25 cycloalkenyl, C1-25 aryloxy, C1-25 cycloalkoxy, C1-25 cycloalkenoxy, N- or S-oxo and N- or S-thioxo;
• R2 is branched or unbranched and substituted or unsubstituted selected from the group consisting of hydrido, C1-10 alkyl, cyano, trifluoromethyl, C6-15 cycloalkyl, C6-30 aryl;
• R3 and R4 form a 4 or 5 membered ring with the N, containing no other heteroatom;
• or one or more hydrates of the one or more compounds in a therapeutically effective amount to increase the activity of Gelatinase A in ocular cells;
• and
• a pharmaceutically acceptable aqueous or non-aqueous carrier for delivery on or within the eye.

A pharmaceutically acceptable composition comprising:

• one or more compounds selected from the following formula:
• a compound selected from the following formulation:
• wherein W is selected from the group consisting of oxygen and sulfur;
• Z is selected from the group consisting of oxygen and sulfur;
• R1 is substituted or unsubstituted C6-25 aryl
• wherein, when R1 is substituted, R1 is substituted with one or more substituents selected from the group consisting of C1-25 alkyl, C1-25 alkenyl, C1-25 alkynyl, C1-25 alkoxy, C1-25 alkenoxy, hydroxy, carboxy, amino, C1-25 (N-alkylcarbonyl)amino, C1-25 (N-alkylcarbonyl)-N-alkylamino, C1-25 (N-alkylcarbonylalkyl)amino, cyano, nitro, sulfo, sulfino, sulfhydryl, halo, C1-25 haloalkyl, trifluoromethyl, C1-25 trifluoromethylalkyl, C6-30 arylalkyl, C6-30 aryl, C1-25 N-alkylamino, C1-25 N-dialkylamino, C1-25 (N-alkyl-N-alkenyl)amino, C1-25 N-dialkenylamino, C1-25 alkylsulfonyl, C1-25 alkylsulfinyl, C1-25 alkylthio, hydrido, C1-25 cyanoalkyl, C1-25 acyl, C1-25 alkylcarbonyloxy, nitroso, C1-25 alkoxyalkyl, C1-25 alkoxycarbonyl, C1-25 hydroxyalkyl, thiocarboxy, C1-25 thiocarboxyalkyl, C1-25 alkylthiocarbonyl, C1-25 alkylthiocarbonylalkyl, C1-25 alkoxythiocarbonyl, C1-25 alkoxythiocarbonylalkyl, sulfamoyl, sulfinamoyl, C1-25 N-alkylsulfamoyl, C1-25 N-dialkylsulfamoyl, C1-25 N-alkylsulfamoyl, C1-25 N-dialkylsulfinamoyl, C1-25 sulfamoylalkyl, C1-25 sulfinamoylalkyl, aminocarbonyl, C1-25 aminocarbonylalkyl aminocarbonylmethyl, C1-25 N-alkylaminocarbonyl, C1-25 N-dialkylaminocarbonyl, C1-25 alkoxycarbonylamino, thiocarbamoyl, C1-25 thiocarbamoylalkyl, C1-25 (N-alkyl)thiocarbamoyl, C1-25 (N-dialkyl)thiocarbamoyl, aminothio, C1-25 alkylaminothio, C1-25 N-dialkylaminothio, C1-25 cycloalkyl, C1-25 cycloalkenyl, C1-25 aryloxy, C1-25 cycloalkoxy, C1-25 cycloalkenoxy, N- or S-oxo and N- or S-thioxo;
• R2 is branched or unbranched and substituted or unsubstituted selected from the group consisting of hydrido, C1-10 alkyl, cyano, trifluoromethyl, C6-15 cycloalkyl, C6-30 aryl;
• wherein R3 and R4 form a 4 or 5 membered ring with the N, containing no other heteroatom;
• or one or more acid addition salts of the in a therapeutically effective amount to increase the activity of Gelatinase A in ocular cells and a pharmaceutically acceptable aqueous or non-aqueous carrier for delivery on or within the eye.

A pharmaceutically acceptable composition comprising:

• one or more compounds defined by the following formula:
• wherein W is selected from the group consisting of oxygen and sulfur;
• Z is selected from the group consisting of oxygen and sulfur;
• R1 is a substituted or unsubstituted C6-25 aryl
• wherein when R1 is substituted, R1 is substituted with one or more substituents selected from the group consisting of C1-25 alkyl, C1-25 alkenyl, C1-25 alkynyl, C1-25 alkoxy, C1-25 alkenoxy, hydroxy, carboxy, amino, C1-25 (N-alkylcarbonyl)amino, C1-25 (N-alkylcarbonyl)-N-alkylamino, C1-25 (N-alkylcarbonylalkyl)amino, cyano, nitro, sulfo, sulfino, sulfhydryl, halo, C1-25 haloalkyl, trifluoromethyl, C1-25 trifluoromethylalkyl, C6-30 arylalkyl, C6-30 aryl, C1-25 N-alkylamino, C1-25 N-dialkylamino, C1-25 (N-alkyl-N-alkenyl)amino, C1-25 N-dialkenylamino, C1-25 alkylsulfonyl, C1-25 alkylsulfinyl, C1-25 alkylthio, hydrido, C1-25 cyanoalkyl, C1-25 acyl, C1-25 alkylcarbonyloxy, nitroso, C1-25 alkoxyalkyl, C1-25 alkoxycarbonyl, C1-25 hydroxyalkyl, thiocarboxy, C1-25 thiocarboxyalkyl, C1-25 alkylthiocarbonyl, C1-25 alkylthiocarbonylalkyl, C1-25 alkoxythiocarbonyl, C1-25 alkoxythiocarbonylalkyl, sulfamoyl, sulfinamoyl, C1-25 N-alkylsulfamoyl, C1-25 N-dialkylsulfamoyl, C1-25 N-alkylsulfinamoyl, C1-25 N-dialkylsulfinamoyl, C1-25 sulfamoylalkyl, C1-25 sulfinamoylalkyl, aminocarbonyl, C1-25 aminocarbonylalkyl aminocarbonylmethyl, C1-25 N-alkylaminocarbonyl, C1-25 N-dialkylaminocarbonyl, C1-25 alkoxycarbonylamino, thiocarbamoyl, C1-25 thiocarbamoylalkyl, C1-25 (N-alkyl)thiocarbamoyl, C1-25 (N-dialkyl)thiocarbamoyl, aminothio, C1-25 alkylaminothio, C1-25 N-dialkylaminothio, C1-25 cycloalkyl, C1-25 cycloalkenyl, C1-25 aryloxy, C1-25 cycloalkoxy, C1-25 cycloalkenoxy, N- or S-oxo and N- or S-thioxo;
• R2 is branched or unbranched and substituted or unsubstituted selected from the group consisting of hydrido, C1-10 alkyl, cyano, trifluoromethyl, C6-15 cycloalkyl, C6-30 aryl;
• R3 and R4 form a 4 or 5 membered ring with the N, containing no other heteroatom;
• or one or more base addition salts of the one or more compounds in a therapeutically effective amount to increase the activity of Gelatinase A in ocular cells;
• and
• a pharmaceutically acceptable aqueous or non-aqueous carrier for delivery on or within the eye.