ALDH-2 INHIBITORS IN THE TREATMENT OF DRUG ADDICTION

1 . A compound of the formula:

wherein:

R 1 is optionally substituted phenyl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;

R2 is hydrogen, hydroxy, halogen, optionally substituted lower alkoxy, optionally substituted lower alkyl, cyano, optionally substituted heteroaryl, C(O)OR 5 , —C(O)R 5 , —SO 2 R 15 , —B(OH) 2 , —OP(O)(OR 5 ) 2 , C(NR 20 )NHR 22 , —NHR 4 , or —C(O)NHR 5 , in which,

R 4 is hydrogen, —C(O)NHR 5 , or —SO 2 R 15 , or —C(O)R 5 ;

R 5 is hydrogen, optionally substituted lower alkyl;

R 15 is optionally substituted lower alkyl or optionally substituted phenyl; or

R 2 is —O-Q-R 6 , in which Q is a covalent bond or lower alkylene and R 6 is optionally substituted heteroaryl;

R 3 is hydrogen, cyano, optionally substituted amino, lower alkyl, lower alkoxy, or halo;

X, Y and Z are chosen from —CR 7 — and —N—, in which R 7 is hydrogen, lower alkyl, lower alkoxy, or halo;

V is oxygen, sulfur, or —NH—; and

W is -Q 1 -T-Q 2 -, wherein

Q 1 is a covalent bond or C 1-6 linear or branched alkylene optionally substituted with hydroxy, lower alkoxy, amino, cyano, or ═O;

Q 2 is C 1-6 linear or branched alkylene optionally substituted with hydroxy, lower alkoxy, amino, cyano, or ═O; and

T is a covalent bond, —O—, or —NH—, or

T and Q 1 may together form a covalent bond,

R 20 and R 22 are independently selected from the group consisting of hydrogen, hydroxy, C 1-15 alkyl, C 2-15 alkenyl, C 2-15 alkynyl, cycloalkyl, heterocyclyl, aryl, benzyl, and heteroaryl,

wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, benzyl, and heteroaryl moieties are optionally substituted with from 1 to 3 substituents independently selected from halo, alkyl, mono- or dialkylamino, alkyl or aryl or heteroaryl amide, CN, O—C 1-6 alkyl, CF 3 , COOH, OCF 3 , B(OH) 2 , Si(CH 3 ) 3 , aryl, and heteroaryl.

2 . The compound of claim 1 wherein,

R 1 is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, ═O, B(OH) 2 , NO 2 , CF 3 , OCF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SO 2 NR 20 COR 22 , SO 2 NR 20 CO 2 R 22 , SO 2 NR 20 CON(R 20 ) 2 , NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , NR 20 C(NR 20 )NHR 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , C(O)N(R 20 ) 2 , C(S)N(R 20 ) 2 , C(O)NR 2 SO 2 R 22 , NR 20 SO 2 R 22 , SO 2 NR 20 CO 2 R 22 , OCONR 20 SO 2 R 22 , OC(O)R 20 , C(O)OCH 2 OC(O)R 20 , and OCON(R 20 ) 2 , and

further wherein each optional alkyl, cycloalkyl, heteroaryl, aryl, and heterocyclyl substituent is further optionally substituted with aryl, heteroaryl, halo, NO 2 , alkyl, ═O, B(OH) 2 , CF 3 , OCF 3 , Si(CH 3 ) 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NR 20 COR 22 , NR 20 SO 2 R 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , C(O)N(R 20 ) 2 , C(S)N(R 20 ) 2 , NR 20 CON(R 20 ) 2 , OC(O)R 20 , OC(O)N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SR 20 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , CN, or OR 20 .

3 . The compound of claim 2 , wherein X, Y, and Z are —CH—.

4 . The compound of claim 3 wherein,

R 2 and R 3 are independently alkyl, amino, —B(OH) 2 , —C(NR 20 )NHR 22 , —C(O)NHR 5 , —C(O)R 5 , —C(O)OR 5 , cyano, hydrogen, halogen, lower alkoxy, —NHSO 2 R 15 , hydroxy, —OP(O)(OR 5 ) 2 , or —SO 2 R 5 .

5 . The compound of claim 4 , wherein V is —O—.

6 . The compound of claim 5 , wherein Q 1 and/or Q 2 is branch alkylene.

7 . The compound of claim 5 , wherein Q 1 and T together form a covalent bond and Q 2 is methylene so that W is methylene.

8 . The compound of claim 7 , wherein R 2 is hydroxy or —NHSO 2 CH 3 and R 3 is hydrogen.

9 . The compound of claim 7 , where in R 1 is phenyl optionally substituted with one to three members selected from lower alkyl, B(OH) 2 , C(O)N(R 20 ) 2 , C(S)N(R 20 ) 2 , CF 3 , CN, CON(R 20 ) 2 , COOR 20 , halogen, heteroaryl, OCF 3 , OR 20 , and phenyl optionally substituted with 1 to 3 members selected from CF 3 , halogen, OR 20 , CN, heteroaryl, C(O)OR 20 , and lower alkyl.

10 . The compound of claim 7 selected from the group consisting of:

3-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoic acid;

methyl 3-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

methyl 3-((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

4-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)phenyl propionate;

methyl 4-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

4-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoic acid;

3-((3-(4-aminophenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoic acid;

allyl 3-((3-(4-aminophenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

allyl 3-((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

3-((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoic acid;

methyl 3-((3-(4-(2-amino-2-oxoethoxy)phenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

methyl 3-((3-(4-acetoxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

isopropyl 3-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoate;

3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}benzenecarbonitrile;

3-(4-hydroxyphenyl)-7-[(3-(1H-1,2,3,4-tetrazol-5-yl)phenyl)methoxy]chromen-4-one;

3-(4-hydroxyphenyl)-7-{[3-(trifluoromethyl)phenyl]methoxy}chromen-4-one;

7-{[3-fluoro-5-(trifluoromethyl)phenyl]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

prop-2-enyl 3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}benzoate;

3-{[3-(4-aminophenyl)-4-oxochromen-7-yloxy]methyl}benzenecarbonitrile;

3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}benzamide;

3-[(3-{4-[(methylsulfonyl)amino]phenyl}-4-oxochromen-7-yloxy)methyl]benzamide;

3-[(3-{4-[(methylsulfonyl)amino]phenyl}-4-oxochromen-7-yloxy)methyl]benzenecarbonitrile;

methylethyl 3-[(3-{4-[(methylsulfonyl)amino]phenyl}-4-oxochromen-7-yloxy)methyl]benzoate;

3-{4-[(methylsulfonyl)amino]phenyl}-7-{[3-(trifluoromethyl)phenyl]methoxy}chromen-4-one;

3-{[3-(4-aminophenyl)-4-oxochromen-7-yloxy]methyl}benzamide;

3-(4-hydroxyphenyl)-7-{[3-(trifluoromethoxy)phenyl]methoxy}chromen-4-one;

3-(4-aminophenyl)-7-{[3-(trifluoromethyl)phenyl]methoxy}chromen-4-one;

3-(4-aminophenyl)-7-{[3-(trifluoromethoxy)phenyl]methoxy}chromen-4-one;

3-{4-[(methylsulfonyl)amino]phenyl}-7-{[3-(trifluoromethoxy)phenyl]methoxy}chromen-4-one;

methylethyl 3-{[3-(4-aminophenyl)-4-oxochromen-7-yloxy]methyl}benzoate;

methyl 3-({3-[4-(hydroxymethyl)phenyl]-4-oxochromen-7-yloxy}methyl)benzoate;

methyl 3-({3-[4-(dihydroxyboramethyl)phenyl]-4-oxochromen-7-yloxy}methyl)benzoate;

3,3-dimethyl-3-silabutyl 3-{[3-(4-carbamoylphenyl)-4-oxochromen-7-yloxy]methyl}benzoate;

3,3-dimethyl-3-silabutyl 3-[(3-{3-[(methylsulfonyl)amino]phenyl}-4-oxochromen-7-yloxy)methyl]benzoate;

3,3-dimethyl-3-silabutyl 3-{[3-(3-cyanophenyl)-4-oxochromen-7-yloxy]methyl}benzoate;

methyl 3-{[3-(4-{[(4-methylphenyl)sulfonyl]amino}phenyl)-4-oxochromen-7-yloxy]methyl}benzoate;

methyl 3-({3-[4-(amino(hydroxyimino)methyl)phenyl]-4-oxochromen-7-yloxy}methyl)benzoate;

3-[(2-hydroxy-3-{4-[(methylsulfonyl)amino]phenyl}-4-oxochroman-7-yloxy)methyl]benzoic acid;

3-{[3-(4-carbamoylphenyl)-4-oxochromen-7-yloxy]methyl}benzoic acid, methanol, methanol;

3-({3-[4-(methylsulfonyl)phenyl]-4-oxochromen-7-yloxy}methyl)benzoic acid;

4-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)phenylboronic acid;

3-((3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)methyl)phenylboronic acid;

N-{[4-chloro-3-(trifluoromethyl)phenyl]methyl}(3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}phenyl)carboxamide;

(3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}phenyl)-N-{[3-(trifluoromethyl)phenyl]methyl}carboxamide;

methylethyl 3-{[3-(4-carbamoylphenyl)-4-oxochromen-7-yloxy]methyl}benzoate;

2-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}benzenecarbonitrile; and

4-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}benzenecarbonitrile.

11 . The compound of claim 7 , where in R 1 is heteroaryl optionally substituted with one to three members selected from lower alkyl, B(OH) 2 , C(O)N(R 20 ) 2 , C(S)N(R 20 ) 2 , CF 3 , CN, CON(R 20 ) 2 , COOR 20 , halogen, heteroaryl, OCF 3 , OR 20 , and phenyl optionally substituted with 1 to 3 members selected from CF 3 , halogen, OR 20 , CN, heteroaryl, C(O)OR 20 , and lower alkyl.

12 . The compound of claim 11 , wherein R 1 is selected from the group consisting of oxadiazole, oxazole, pyrazole, thiazole, pyridine, indolizinyl, benzothiazolyl, benzothienyl, thiadiazole, pyrrole, imidazole, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthylpyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, thiazole, isothiazole, phenazine, oxazole, isoxazole, phenoxazine, phenothiazine, imidazolidine, and imidazoline.

13 . The compound of claim 12 , wherein R 1 is optionally substituted oxadiazole.

14 . The compound of claim 13 , selected from the group consisting of:

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

3-(4-hydroxyphenyl)-7-((5-phenyl-1,2,4-oxadiazol-3-yl)methoxy)-4H-chromen-4-one;

3-(4-hydroxyphenyl)-6-((3-(3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methoxy)-4H-chromen-4-one;

3-(4-hydroxyphenyl)-7-((3-phenyl-1,2,4-oxadiazol-5-yl)methoxy)-4H-chromen-4-one;

N-(4-(4-oxo-7-((5-(3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)methoxy)-4H-chromen-3-yl)phenyl)methanesulfonamide;

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

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

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

N-(4-(7-((5-(3-fluoro-5-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)methoxy)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide;

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

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

7-((5-(2,5-bis(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)methoxy)-3-(4-hydroxyphenyl)-4H-chromen-4-one;

7-({5-[3,5-bis(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-methoxyphenyl)-7-{[5-(2-methoxyphenyl)(1,2,4-oxadiazol-3-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-2-(trifluoromethyl)-6-({5-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one;

3-(4-hydroxyphenyl)-6-({5-[4-methoxy-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-2-(trifluoromethyl)chromen-4-one;

6-({5-[3-fluoro-5-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-3-(4-hydroxyphenyl)-2-(trifluoromethyl)chromen-4-one;

3-(3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}-1,2,4-oxadiazol-5-yl)benzenecarbonitrile;

3-(4-hydroxyphenyl)-7-{[5-(3-(1H-1,2,3,4-tetraazol-5-yl)phenyl)(1,2,4-oxadiazol-3-yl)]methoxy}chromen-4-one;

3-(3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}-1,2,4-oxadiazol-5-yl)benzoic acid;

prop-2-enyl 3-(3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}-1,2,4-oxadiazol-5-yl)benzoate;

7-{[5-(3-fluorophenyl)(1,2,4-oxadiazol-3-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

methylethyl 3-(3-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}-1,2,4-oxadiazol-5-yl)benzoate;

7-{[5-(3-fluorophenyl)(1,3,4-oxadiazol-2-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyl](1,3,4-oxadiazol-2-yl)}methoxy)chromen-4-one;

3-[7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-4-oxochromen-3-yl]benzenecarbonitrile;

7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-3-{3-[(methylsulfonyl)amino]phenyl}chromen-4-one;

7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-3-[4-(methylsulfonyl)phenyl]chromen-4-one;

4-[7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-4-oxochromen-3-yl]benzenecarbonitrile;

4-[7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-4-oxochromen-3-yl]benzamide;

3-(3-acetylphenyl)-7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one;

7-({5-[3-fluoro-5-(trifluoromethyl)phenyl](1,3,4-oxadiazol-2-yl)}methoxy)-3-(4-hydroxyphenyl)chromen-4-one;

methyl 3-[7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-4-oxochromen-3-yl]benzoate;

7-({3-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-fluorophenyl)-7-{[5-(2-methoxyphenyl)(1,2,4-oxadiazol-3-yl)]methoxy}chromen-4-one;

3-(4-methylphenyl)-7-({5-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one;

4-[4-oxo-7-({5-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-3-yl]benzenecarbonitrile;

3-(3-fluorophenyl)-7-({5-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one;

7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one;

7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-3-(4-{[(4-methylphenyl)sulfonyl]amino}phenyl)chromen-4-one;

7-{[5-(3-chlorophenyl)(1,3,4-oxadiazol-2-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{[5-(4-fluorophenyl)(1,3,4-oxadiazol-2-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-3-[4-(hydroxymethyl)phenyl]chromen-4-one;

4-[7-({5-[3-fluoro-5-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-4-oxochromen-3-yl]benzoic acid;

2-fluoro-5-[7-({5-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)-4-oxochromen-3-yl]benzenecarbonitrile;

7-({3-[2-fluoro-4-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}ethoxy)-3-{4-[(methylsulfonyl)amino]phenyl}chromen-4-one;

3-[4-(dihydroxyboramethyl)phenyl]-7-({3-[2-fluoro-4-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}ethoxy)chromen-4-one;

7-{[5-(4-fluorophenyl)(1,2,4-oxadiazol-3-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{[5-(4-fluorophenyl)(1,2,4-oxadiazol-3-yl)]methoxy}-3-{4-[(methylsulfonyl)amino]phenyl}chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(3-pyridyl)(1,3,4-oxadiazol-2-yl))methoxy]chromen-4-one;

7-{[5-(4-fluorophenyl)(1,3,4-oxadiazol-2-yl)]ethoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(3-pyridyl)(1,3,4-oxadiazol-2-yl))ethoxy]chromen-4-one;

3-(4-hydroxyphenyl)-7-[(3-(3-pyridyl)(1,2,4-oxadiazol-5-yl))methoxy]chromen-4-one;

3-(4-hydroxyphenyl)-7-({3-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}methoxy)chromen-4-one;

7-({3-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}methoxy)-3-[4-({3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}methoxy)phenyl]chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(4-pyridyl)(1,3,4-oxadiazol-2-yl))ethoxy]chromen-4-one;

3-[4-(dihydroxyboramethyl)phenyl]-7-{[5-(4-fluorophenyl)(1,2,4-oxadiazol-3-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(4-pyridyl)(1,2,4-oxadiazol-3-yl))ethoxy]chromen-4-one;

7-{[5-(4-fluorophenyl)(1,3,4-oxadiazol-2-yl)]methoxy}-3-{4-[(methylsulfonyl)amino]phenyl}chromen-4-one;

7-{[3-(3-aminophenyl)(1,2,4-oxadiazol-5-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(3-pyridyl)(1,2,4-oxadiazol-3-yl))ethoxy]chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(3-pyridyl)(1,2,4-oxadiazol-3-yl))methoxy]chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(2-pyridyl)(1,2,4-oxadiazol-3-yl))methoxy]chromen-4-one;

7-{[3-(5-bromo(3-pyridyl))(1,2,4-oxadiazol-5-yl)]ethoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(2-pyridyl)(1,2,4-oxadiazol-3-yl))ethoxy]chromen-4-one;

7-((1R)-1-{3-[3-fluoro-5-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one;

7-({3-[3-fluoro-5-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}methoxy)-3-(4-hydroxyphenyl)chromen-4-one;

7-((1S)-1-{3-[3-fluoro-5-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one;

7-((1R)-1-{3-[3-fluoro-5-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one;

7-(1-{3-[3-fluoro-5-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}-isopropoxy)-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-{[5-(2-methoxyphenyl)(1,3,4-oxadiazol-2-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{[5-(4-methoxyphenyl)(1,3,4-oxadiazol-2-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{[5-(2-methylphenyl)(1,3,4-oxadiazol-2-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{[5-(3-methylphenyl)(1,3,4-oxadiazol-2-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{[5-(4-methylphenyl)(1,3,4-oxadiazol-2-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-({5-[4-(trifluoromethyl)phenyl](1,3,4-oxadiazol-2-yl)}methoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-{[5-(4-methoxyphenyl)(1,2,4-oxadiazol-3-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{[5-(3-methoxyphenyl)(1,2,4-oxadiazol-3-yl)]methoxy}chromen-4-one;

7-{[5-(4-chlorophenyl)(1,3,4-oxadiazol-2-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{[5-(2-chlorophenyl)(1,3,4-oxadiazol-2-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one; and

3-(4-hydroxyphenyl)-7-{[5-(3-methoxyphenyl)(1,3,4-oxadiazol-2-yl)]methoxy}chromen-4-one.

15 . The compound of claim 12 , wherein R 1 is optionally substituted oxazole.

16 . The compound of claim 15 , selected from the group consisting of:

3-(4-hydroxyphenyl)-7-[(2-phenyl(1,3-oxazol-4-yl))methoxy]chromen-4-one;

7-({5-[3,5-bis(trifluoromethyl)phenyl]isoxazol-3-yl}methoxy)-3-(4-hydroxyphenyl)chromen-4-one;

3-{4-[(methylsulfonyl)amino]phenyl}-7-[(2-phenyl(1,3-oxazol-4-yl))methoxy]chromen-4-one;

3-(4-hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyl]isoxazol-3-yl}methoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-({3-[3-(trifluoromethyl)phenyl]isoxazol-5-yl}methoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-phenylisoxazol-3-yl)methoxy]chromen-4-one;

3-(4-hydroxyphenyl)-7-({2-[3-(trifluoromethyl)phenyl](1,3-oxazol-4-yl)}methoxy)chromen-4-one;

7-{[5-(4-chlorophenyl)isoxazol-3-yl]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{[5-(3,4-dichlorophenyl)isoxazol-3-yl]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-({2-[5-fluoro-3-(trifluoromethyl)phenyl](1,3-oxazol-4-yl) } methoxy)-3-(4-hydroxyphenyl)chromen-4-one;

methyl 2-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}-1,3-oxazole-4-carboxylate;

2-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}-1,3-oxazole-4-carboxylic acid;

(2-{[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]methyl}(1,3-oxazol-4-yl))-N-methylcarboxamide;

7-{[2-(4-chlorophenyl)(1,3-oxazol-4-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{[2-(3,4-difluorophenyl)(1,3-oxazol-4-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{[2-(3,5-difluorophenyl)(1,3-oxazol-4-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{[2-(4-fluorophenyl)(1,3-oxazol-4-yl)]methoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-{[2-(3,4,5-trifluorophenyl)(1,3-oxazol-4-yl)]methoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-[(5-(2-pyridyl)isoxazol-3-yl)methoxy]chromen-4-one;

7-(3-{2-[3-fluoro-5-(trifluoromethyl)phenyl](1,3-oxazol-4-yl)}propoxy)-3-(4-hydroxyphenyl)chromen-4-one; and

4-[7-({2-[5-fluoro-3-(trifluoromethyl)phenyl](1,3-oxazol-4-yl)}methoxy)-4-oxochromen-3-yl]phenyl dihydrogen phosphate.

17 . The compound of claim 12 , wherein R 1 is optionally substituted thiazole.

18 . The compound of claim 17 , selected from the group consisting of:

3-{4-[(methylsulfonyl)amino]phenyl}-7-({4-methyl-2-[4-(trifluoromethyl)phenyl](1,3-thiazol-5-yl)}methoxy)chromen-4-one;

ethyl 4-[7-({4-methyl-2-[4-(trifluoromethyl)phenyl](1,3-thiazol-5-yl)}methoxy)-4-oxochromen-3-yl]benzoate;

methyl 3-[7-({4-methyl-2-[4-(trifluoromethyl)phenyl](1,3-thiazol-5-yl)}methoxy)-4-oxochromen-3-yl]benzoate;

3-(4-hydroxyphenyl)-7-({4-methyl-2-[4-(trifluoromethyl)phenyl](1,3-thiazol-5-yl)}methoxy)chromen-4-one;

3-(4-{[(4-methylphenyl)sulfonyl]amino}phenyl)-7-({4-methyl-2-[4-(trifluoromethyl)phenyl](1,3-thiazol-5-yl)}methoxy)chromen-4-one; and

3-{4-[(methylsulfonyl)amino]phenyl}-7-({2-[4-(trifluoromethyl)phenyl]( 1,3-thiazol-4-yl)}methoxy)chromen-4-one.

19 . The compound of claim 12 , wherein R 1 is optionally substituted pyridine.

20 . The compound of claim 19 , selected from the group consisting of:

3-(4-hydroxyphenyl)-7-(4-pyridylmethoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-(2-pyridylmethoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-{[6-(trifluoromethyl)(3-pyridyl)]methoxy}chromen-4-one;

7-{[6-(trifluoromethyl)(3-pyridyl)]methoxy}-3-(4-{[6-(trifluoromethyl)(3-pyridyl)]methoxy}phenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-[(6-pyrazolyl(3-pyridyl))methoxy]chromen-4-one; and

3-(4-hydroxyphenyl)-7-(3-pyridylmethoxy)chromen-4-one.

21 . The compound of claim 12 , wherein R 1 is optionally substituted pyrazole.

22 . The compound of claim 21 , selected from the group consisting of:

7-{2-[4-(4-chlorophenyl)pyrazolyl]ethoxy}-3-(4-hydroxyphenyl)chromen-4-one;

ethyl 1-{2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]ethyl}pyrazole-4-carboxylate; and

3-(4-hydroxyphenyl)-7-{2-[3-(trifluoromethyl)pyrazolyl]ethoxy}chromen-4-one.

23 . The compound of claim 7 , where in R 1 is heterocycyl optionally substituted with one to three members selected from lower alkyl, B(OH) 2 , C(O)N(R 20 ) 2 , C(S)N(R 20 ) 2 , CF 3 , CN, CON(R 20 ) 2 , COOR 20 , halogen, heteroaryl, OCF 3 , OR 20 , and phenyl optionally substituted with 1 to 3 members selected from CF 3 , halogen, OR 20 , CN, heteroaryl, C(O)OR 20 , and lower alkyl.

24 . The compound of claim 14 , wherein R 1 is selected from the group consisting of tetrahydrofuranyl, morpholino, oxathiane, thiomorpholino, tetraydropthiophenyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, triazolidino, piperazinyl, dihydropyridino, pyrrolidinyl, imidazolidino, hexahydropyrimidine, hezahydropyridazine, and imidazoline.

25 . The compound of claim 24 , wherein R 1 is piperazinyl.

26 . The compound of claim 25 , selected from the group consisting of:

3-(4-hydroxyphenyl)-7-{2-[4-(4-methoxyphenyl)piperazinyl]ethoxy}chromen-4-one;

7-{2-[4-(4-fluorophenyl)piperazinyl]ethoxy}-3-(4-hydroxyphenyl)chromen-4-one;

7-{2-[4-(3-chlorophenyl)piperazinyl]ethoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-(2-{4-[3-(trifluoromethyl)phenyl]piperazinyl}ethoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-(2-piperazinylethoxy)chromen-4-one;

N-(3-fluorophenyl)(4-{2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]ethyl}piperazinyl)carboxamide;

7-[2-(4-{[(4-fluorophenyl)amino]thioxomethyl}piperazinyl)ethoxy]-3-(4-hydroxyphenyl)chromen-4-one;

N-(2,4-difluorophenyl)(4-{2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]ethyl}piperazinyl)carboxamide;

7-{2-[4-(2-fluorophenyl)piperazinyl]ethoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-{2-[4-(2-methylphenyl)piperazinyl]ethoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{2-[4-(2-methoxyphenyl)piperazinyl]ethoxy}chromen-4-one;

7-{2-[4-(3-fluorophenyl)piperazinyl]ethoxy}-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-{2-[4-(3-methylphenyl)piperazinyl]ethoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{2-[4-(3-methoxyphenyl)piperazinyl]ethoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-(2-{4-[4-(trifluoromethyl)phenyl]piperazinyl}ethoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-{2-[4-(4-methylphenyl)piperazinyl]ethoxy}chromen-4-one; and

3-(4-hydroxyphenyl)-7-(2-{4-[2-(trifluoromethyl)phenyl]piperazinyl}ethoxy)chromen-4-one.

27 . The compound of claim 5 , wherein R 3 is hydrogen.

28 . The compound of claim 27 , where in R 1 is phenyl optionally substituted with one to three members selected from lower alkyl, B(OH) 2 , C(O)N(R 20 ) 2 , C(S)N(R 20 ) 2 , CF 3 , CN, CON(R 20 ) 2 , COOR 20 , halogen, heteroaryl, OCF 3 , OR 20 , and phenyl optionally substituted with 1 to 3 members selected from CF 3 , halogen, OR 20 , CN, heteroaryl, C(O)OR 20 , and lower alkyl.

29 . The compound of claim 28 , wherein T is a covalent bond.

30 . The compound of claim 29 selected from the group consisting of:

7-[2-(4-fluorophenyl)-2-oxoethoxy]-3-(4-methoxyphenyl)chromen-4-one;

7-[2-(4-fluorophenyl)-2-oxoethoxy]-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-{[3-(trifluoromethyl)phenyl]ethoxy}chromen-4-one;

7-[2-(3-fluorophenyl)-2-oxoethoxy]-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-{2-oxo-2-[4-(trifluoromethyl)phenyl]ethoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-{2-oxo-2-[2-(trifluoromethyl)phenyl]ethoxy}chromen-4-one;

3-(4-hydroxyphenyl)-7-(2-phenylethoxy)chromen-4-one;

3-(4-hydroxyphenyl)-7-(3-phenylpropoxy)chromen-4-one;

7-((2S)-2-hydroxy-3-phenylpropoxy)-3-(4-hydroxyphenyl)chromen-4-one; and

7-[2-(4-fluorophenyl)ethoxy]-3-(4-hydroxyphenyl)chromen-4-one.

31 . The compound of claim 28 , wherein T is —NH— or —O—.

32 . The compound of claim 31 selected from the group consisting of:

2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]-n-[3-(trifluoromethyl)phenyl]acetamide;

7-(3-{[(3,5-difluorophenyl)methyl]amino}-2-hydroxypropoxy)-3-(4-methoxyphenyl)chromen-4-one;

7-[(2S)-2-hydroxy-3-({[3-(trifluoromethyl)phenyl]methyl}amino)propoxy]-3-(4-methoxyphenyl)chromen-4-one;

2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]-N-[2-(trifluoromethyl)phenyl]acetamide;

N-[(1S)-1-(4-fluorophenyl)ethyl]-2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]acetamide;

N-(3-fluorophenyl)-2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]acetamide;

7-[(2S)-2-hydroxy-3-({[3-(trifluoromethyl)phenyl]methyl}amino)propoxy]-3-(4-hydroxyphenyl)chromen-4-one;

3-(4-hydroxyphenyl)-7-[2-({[3-(trifluoromethyl)phenyl]methyl}amino)ethoxy]chromen-4-one;

7-((2S)-3-{[(3,5-difluorophenyl)methyl]amino}-2-hydroxypropoxy)-3-(4-hydroxyphenyl)chromen-4-one;

N-[(1R)-1-(4-fluorophenyl)ethyl]-2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yloxy]acetamide;

7-(2-{[(4-fluorophenyl) ethyl]amino}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one; and

7-[2-(4-chlorophenoxy)ethoxy]-3-(4-hydroxyphenyl)chromen-4-one.

33 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

34 . A method of treating chemical dependency on an dopamine-producing agent, comprising administering a therapeutically effective dose of the compound of claim 1 to a mammal in need thereof.

35 . The method of claim 34 , wherein the dopamine-producing agent is selected from the group consisting of cocaine, opiates, amphetamines, nicotine, and alcohol.

36 . The method of claim 35 , wherein the compound of claim 1 is 3-[(3-{4-[(methylsulfonyl)amino]phenyl}-4-oxochromen-7-yloxy)methyl]benzoic acid.

37 . The compound of claim 10 wherein the compound is 3-((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoic acid.

38 . The pharmaceutical composition of claim 33 , wherein the compound of claim 1 is 3-((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yloxy)methyl)benzoic acid.