S-nitrosoglutathione reductase inhibitors

1. The compound of formula (I)

wherein

X is selected from the group consisting of O and S;

Y is selected from the group consisting of O and S;

Z is selected from the group consisting of Z 1 , Z 2 , Z 3 , and Z 4 , wherein

Z 1 is

Z 2 is

Z 3 is

and

Z 4 is

provided that Z is only Z 4 when at least one of X or Y is S;

R 1 is selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 1 -C 6 )haloalkyl, unsubstituted aryl(C 1 -C 4 )alkyl, substituted aryl(C 1 -C 6 )alkyl, (C 1 -C 6 )heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

R 2 is selected from the group consisting of hydrogen, halogen, cyano, and (C 1 -C 6 ) alkoxy;

R 3 is selected from the group consisting of hydrogen, halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, cyano, and N,N-dimethylamino;

R 4 is selected from the group consisting of tetrazole, oxadiazolone, thiadiazolone, methylsulfonylcarbamoyl, and N-hydroxycarbamoyl; and

R 5 is selected from the group consisting of carboxy, tetrazole, oxadiazolone, thiadiazolone, methylsulfonylcarbamoyl, and N-hydroxycarbamoyl.

2. The compound of claim 1 wherein

R 4 is selected from the group consisting of tetrazole, 1,2,4-oxadiazol-5(4H)-one-3-yl, 1,2,4-thiadiazol-5(4H)-one-3-yl, 1,3,4-oxadiazol-2(3H)-one-5-yl, 1,3,4-thiadiazol-2(3H)-one-5-yl, 1,2,4-thiadiazol-3(2H)-one-5-yl, 1,2,4-oxadiazol-3(2H)-one-5-yl, methylsulfonylcarbamoyl, and N-hydroxycarbamoyl; and

R 5 is selected from the group consisting of carboxy, tetrazole, 1,2,4-oxadiazol-5(4H)-one-3-yl, 1,2,4-thiadiazol-5(4H)-one-3-yl, 1,3,4-oxadiazol-2(3H)-one-5-yl, 1,3,4-thiadiazol-2(3H)-one-5-yl, 1,2,4-thiadiazol-3(2H)-one-5-yl, 1,2,4-oxadiazol-3(2H)-one-5-yl, methylsulfonylcarbamoyl, and N-hydroxycarbamoyl.

3. The compound of claim 1 wherein

R 1 is selected from the group consisting of hydrogen, CF 3 , CF 2 H, CF 2 CH 3 , CF 2 CH 2 CH 3 , methyl, isopropyl, isobutyl, cyclopentyl, CH 2 OCH 3 , SCH 3 , benzyl, 4-carboxy benzyl, thiophen-2-yl, and thiophen-3-yl;

R 2 is selected from the group consisting of hydrogen, fluoro, chloro, methoxy, and cyano; and

R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, CF 3 , methoxy, cyano, and N,N-dimethylamino.

4. The compound of claim 1 wherein R 1 is selected from the group consisting of hydrogen, CF 3 , CF 2 H, methyl, and 4-carboxybenzyl;

R 2 is selected from the group consisting of hydrogen and fluoro;

R 3 is selected from the group consisting of hydrogen, fluoro, chloro, and methyl;

R 4 is selected from the group consisting of tetrazole, 1,2,4-oxadiazol-5(4H)-one-3-yl, 1,2,4-thiadiazol-5(4H)-one-3-yl, 1,3,4-oxadiazol-2(3H)-one-5-yl, methylsulfonylcarbamoyl, and N-hydroxycarbamoyl; and

R 5 is selected from the group consisting of carboxy, tetrazole, 1,2,4-oxadiazol-5(4H)-one-3-yl, 1,2,4-thiadiazol-5(4H)-one-3-yl, 1,3,4-oxadiazol-2(3H)-one-5-yl, methylsulfonylcarbamoyl, and N-hydroxycarbamoyl.

5. The compound of claim 1 selected from the group consisting of

3-(4-(1H-tetrazol-5-yl)phenyl)-7-hydroxy-2-(trifluoromethyl)-4H-chromen-4-one;

5-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)thiophene-2-carboxylic acid;

(trans)-4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)cyclohexanecarboxylic acid;

(cis)-4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)cyclohexanecarboxylic acid;

3-(4-(1H-tetrazol-5-yl)phenyl)-2-(difluoromethyl)-7-hydroxy-4H-chromen-4-one;

3-(4-(1H-tetrazol-5-yl)phenyl)-7-hydroxy-2-methyl-4H-chromen-4-one;

4-(2-(4-carboxybenzyl)-7-hydroxy-4-oxo-4H-thiochromen-3-yl)benzoic acid;

4-(7-hydroxy-2-methyl-4-oxo-4H-thiochromen-3-yl)benzoic acid;

3-(4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)phenyl)-1,2,4-oxadiazol-5(4H)-one;

4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)-N-(methylsulfonyl)benzamide;

3-(4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)phenyl)-1,2,4-thiadiazol-5(4H)-one;

3-(4-(1H-tetrazol-5-yl)phenyl)-7-hydroxy-2-methyl-4H-thiochromen-4-one;

5-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)thiophene-3-carboxylic acid;

3-((trans)-4-(1H-tetrazol-5-yl)cyclohexyl)-7-hydroxy-2-(trifluoromethyl)-4H-chromen-4-one;

N-hydroxy-4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)benzamide;

3-(2-chloro-4-(1H-tetrazol-5-yl)phenyl)-7-hydroxy-2-(trifluoromethyl)-4H-chromen-4-one;

3-(3-chloro-4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)phenyl)-1,2,4-oxadiazol-5(4H)-one;

3-(3-fluoro-4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)phenyl)-1,2,4-oxadiazol-5(4H)-one;

3-(3-chloro-4-(1H-tetrazol-5-yl)phenyl)-7-hydroxy-2-(trifluoromethyl)-4H-chromen-4-one; and

3-(4-(1H-tetrazol-5-yl)phenyl)-7-hydroxy-4H-chromen-4-one; and

5-(4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)phenyl)-1,3,4-oxadiazol-2(3H)-one.

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any of the previous claims together with a pharmaceutically accepted carrier or excipient.