Methods for Preserving Renal Function Using Xanthine Oxidoreductase Inhibitors

1 . A method of preserving renal function in a subject in need thereof, the method comprising the step of:

administering to the subject a therapeutically effective amount of at least one compound, wherein said at least one compound is a xanthine oxidoreductase inhibitor or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein the xanthine oxidoreductase inhibitor is selected from the group consisting of: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid, 2-[3-cyano-4-(3-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-[3-cyano-4-(2-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, 2-(3-cyano-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid, 2-[4-(2-carboxypropoxy)-3-cyanophenyl]-4-methyl-5-thiazolecarboxylic acid, 1-(3-cyano-4-(2,2-dimethylpropoxy)phenyl)-1H-pyrazole-4-carboxylic acid, 1-3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid, pyrazolo[1,5-a]-1,3,5-triazin- 4 -(1H)-one, 8-[3-methoxy-4-(phenylsulfinyl)phenyl]-sodium salt (±), 3-(2-methyl-4-pyridyl)-5-cyano-4-isobutoxyphenyl)-1,2,4-triazole and a pharmaceutically acceptable salt thereof.

3 . The method of claim 1 , wherein the subject has hyperuricemia, gout, acute gouty arthritis, chronic gouty joint disease, tophaceous gout, uric acid nephropathy or nephrolithiasis.

4 . The method of claim 1 , wherein the subject has a progressive renal disease.

5 . The method of claim 1 , wherein the subject's GFR is maintained at a level of at least approximately 75% or greater when compared to the subject's baseline GFR level.

6 . A method of preserving renal function in a subject in need thereof, the method comprising the step of:

administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:

wherein R 1 and R 2 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C 1 -C 10 alkyl group, an unsubstituted or substituted C 1 -C 10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, a phenylsulfinyl group or a cyano (—CN) group;

wherein R 3 and R 4 are each independently a hydrogen or A, B, C or D as shown below:

wherein T connects A, B, C or D to the aromatic ring shown above at R 1 , R 2 , R 3 or R 4 .

wherein R 5 and R 6 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C 1 -C 10 alkyl group, an unsubstituted or substituted C 1 -C 10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;

wherein R 7 and R 8 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C 1 -C 10 alkyl group, an unsubstituted or substituted C 1 -C 10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;

wherein R 9 is an unsubstituted pyridyl group or a substituted pyridyl group; and

wherein R 10 is a hydrogen or a lower alkyl group, a lower alkyl group substituted with a pivaloyloxy group and in each case, R 10 bonds to one of the nitrogen atoms in the 1,2,4-triazole ring shown above.

7 . The method of claim 6 , wherein the compound is 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid or a pharmaceutically acceptable salt thereof.

8 . The method of claim 6 , wherein the compound is 2-[3-cyano-4-(3-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid or a pharmaceutically acceptable salt thereof.

9 . The method of claim 6 , wherein the compound is 2-[3-cyano-4-(2-hydroxy-2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid or a pharmaceutically acceptable salt thereof.

10 . The method of claim 6 , wherein the compound is 2-(3-cyano-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid or a pharmaceutically acceptable salt thereof.

11 . The method of claim 6 , wherein the compound is 2-[4-(2-carboxypropoxy)-3-cyanophenyl]-4-methyl-5-thiazolecarboxylic acid or a pharmaceutically acceptable salt thereof.

12 . The method of claim 6 , wherein the compound is 1-3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof.

13 . The method of claim 6 , wherein the compound is pyrazolo[1,5-a]-1,3,5-triazin-4-(1H)-one, 8-[3-methoxy-4-(phenylsulfinyl)phenyl]-sodium salt (±).

14 . The method of claim 6 , wherein the compound is 3-(2-methyl-4-pyridyl)-5-cyano-4-isobutoxyphenyl)-1,2,4-triazole or a pharmaceutically acceptable salt thereof.

15 . The method of claim 6 , wherein the subject has hyperuricemia, gout, acute gouty arthritis, chronic gouty joint disease, tophaceous gout, uric acid nephropathy or nephrolithiasis.

16 . The method of claim 6 , wherein the subject has a progressive renal disease.

17 . The method of claim 6 , wherein the subject's GFR is maintained at a level of at least approximately 75% or greater when compared to the subject's baseline GFR level.

18 . A method of preserving renal function in a subject in need of thereof, the method comprising the step of:

administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:

wherein R 11 and R 12 are each independently a hydrogen, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl, or R 11 and R 12 may together form a four- to eight-membered carbon ring together with the carbon atom to which they are attached;

wherein R 13 is a hydrogen or a substituted or unsubstituted lower alkyl group;

wherein R 14 is one or two radicals selected from a group consisting of a hydrogen, a halogen, a nitro group, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted phenyl, —OR 16 and —SO 2 NR 17 R 17′ , wherein R 16 is a hydrogen, a substituted or unsubstituted lower alkyl, a phenyl-substituted lower alkyl, a carboxymethyl or ester thereof, a hydroxyethyl or ether thereof, or an allyl; R 17 and R 17′ are each independently a hydrogen or a substituted or unsubstituted lower alkyl;

wherein R 15 is a hydrogen or a pharmaceutically active ester-forming group;

wherein A is a straight or branched hydrocarbon radical having one to five carbon atoms;

wherein B is a halogen, an oxygen, or a ethylenedithio;

wherein Y is an oxygen, a sulfur, a nitrogen or a substituted nitrogen;

wherein Z is an oxygen, a nitrogen or a substituted nitrogen; and

the dotted line refers to either a single bond, a double bond, or two single bonds.

19 . The method of claim 18 , wherein the subject has hyperuricemia, gout, acute gouty arthritis, chronic gouty joint disease, tophaceous gout, uric acid nephropathy, or nephrolithiasis.

20 . The method of claim 18 , wherein the subject has a progressive renal disease.

21 . The method of claim 18 , wherein the subject's GFR is maintained at a level of at least approximately 75% or greater when compared to the subject's baseline GFR level.