IP Library › Granted Patent US 9,024,032

Granted Patent B2

US 9,024,032 · App. 13/582,601 · Granted May 5, 2015

Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders

Inventors: Scott Wolkenberg (Wyndmoor, PA); James C. Barrow (Arnold, MD); Michael S. Poslusney (Nashville, TN); Scott T. Harrison (Glenside, PA); B. Wesley Trotter (Medfield, MA); James Mulhearn (Elkins Park, PA); Kausik K. Nanda (Norristown, PA); Peter J. Manley (Harleysville, PA); Zhijian Zhao (Wilmington, DE); Jeffrey W. Schubert (Ambler, PA); Nathan Kett (Columbia, TN); Amy Zartman (Hatfield, PA)

Assignee: Merck Sharp & Dohme Corp.

C07D213/69 A61K31/4412 A61K31/4418 A61K31/4439 A61K31/444 A61K31/4545 A61K31/4709 A61K31/4725 A61K31/5377 A61K31/541 A61K31/69 A61K45/06 C07D213/73 C07D213/74 C07D401/10 C07D401/14 C07D413/10 C07D413/12 C07D417/10 C07D471/04 C07F5/025 C07D401/04 C07D401/06

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Quick Facts

Patent No.: US 9,024,032
App. No.: 13/582,601
Granted: May 5, 2015
Kind: B2

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Abstract

The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved.

Claims (635)

1. A compound of structural formula I:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

A represents hydrogen, B(OH) 2 , halo, OH, C 3-10 cycloalkyl, or C 1-6 alkyl;

X represents hydrogen, or C 1-6 alkyl;

Y represents phenyl or pyridyl, any of which is optionally substituted with 1 to 3 groups of R a ;

R 1 represents CH(OH)CH 3 , NH 2 NHCH 3 ,(CHR 2 ) n C 6-10 aryl, or (CHR 2 ) n C 6-10 heterocyclyl, wherein said aryl and heterocyclyl are optionally substituted with 1 to 3 groups of R a ;

each R 2 independently represents H, OH, or C 1-6 alkyl;

each R a independently represents C 1-6 alkyl, halogen, (CH 2 ) n CF 3 , OCHF 2 , OCF 3 , C 3-6 cycloalkyl, O(CH 2 ) n C 3-6 cycloalkyl, NR 2 C(O)R 2 , C(O)N(R 2 ) 2 , C(R 2 ) 2 OR 2 , C(O)R 2 , NO 2 , CN, N(R 2 ) 2 , C(O)OR 2 SO 2 R 2 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, NH(CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl, said cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of R b ;

each R b independently represents C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, (CH 2 ) n CF 3 , —O—, OR 2 , or CN; and

n represents 0 to 5; and

provided that no more than one of said R a is (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 )nC 5-10 heterocyclyl.

2. The compound according to claim 1 represented by structural formula II:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

R 1 represents (CHR 2 ) n C 6-10 aryl, said aryl optionally substituted with 1 to 3 groups of R a ;

each R 2 independently represents H or OH;

each R a is independently selected from C 1-6 alkyl, halogen, (CH 2 ) n CF 3 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n ,C 6-10 aryl, or O(CH 2 ) n ,C 5-10 heterocyclyl, said alkyl, heterocyclyl and aryl are optionally substituted with 1 to 3 groups of R b ;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN.

3. The compound according to claim 2 wherein:

R 1 represents (CHR 2 ) n C 6-10 aryl, and said aryl is phenyl.

4. The compound according to claim 2 wherein

at least one of said 1 to 3 groups of R a is selected from (CH 2 ) n C 5-10 heterocyclyl and (CH 2 ) n C 6-10 aryl, said aryl and heterocyclyl optionally substituted with 1 to 3 groups of R b .

5. The compound according to claim 2 wherein

at least one of said 1 to 3 groups of R a is selected from C 6-10 aryl and C 5-10 heterocyclyl, and said aryl and heterocyclyl are optionally substituted with 1 to 3 groups of R b .

6. The compound according to claim 4 or 5 , wherein

said aryl and heterocyclyl are selected from naphthyridine, indolyl, benzodioxaolyl, pyridyl, furopyridinyl, isoindolyl, pyridooxazinyl, pyrrolopyridinyl, quinoxalinyl, quinazolinyl, quinolinyl, isoquinolinyl, phenyl, indazolyl, [1,2,4]triazolo[1,5-a]pyridine, 1,2,3,4-tetrahydroisoquinoline, 1,3-benzodioxole, 1-benzothiophene, 1H-indazole, 1H-pyrrolo[2,3-b]pyridine, 1H-pyrrolo[2,3-c]pyridine, 1H-pyrrolo[3,2-b]pyridine, 1H-pyrrolo[3,2-c]pyridine, 2,1,3-benzoxadiazole, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine, 3H-imidazo[4,5-b]pyridine, 4,5,6,7-tetrahydropyrazolo [1,5-a]pyridine, furo[2,3-c]pyridine, furo[3,2-b]pyridine, imidazo [1,2-a]pyridine, quinazoline, and thieno[3,2-c]pyridin-4(5H)-one, any of which is optionally substituted with 1 to 3 groups of R b .

7. The compound according to claim 1 , wherein the compound is represented by structural formula II:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

R 1 represents CH(OH)CH 3 ;

R 2 and R 3 are independently selected from H and C 1-6 alkyl;

each R a is independently selected from C 1-6 alkyl, halogen, (CH 2 ) n CF 3 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl, said alkyl, heterocyclyl and aryl are optionally substituted with 1 to 3 groups of R b ;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN; and

n represents 0 to 5.

8. The compound according to claim 7 wherein at least one of said 1 to 3 groups of R a is selected form C 6-10 aryl and C 5-10 heterocyclyl and said ary and heterocyclyl are selected from naphthyridine, indolyl, benzodioxaolyl, pyridyl, furopyridinyl, isoindolyl, pyridooxazinyl, pyrrolopyridinyl, quinoxalinyl, quinazolinyl, quinolinyl, isoquinolinyl, phenyl, indazolyl, [1,2,4]triazolo[1,5-a]pyridine, 1,2,3,4-tetrahydroisoquinoline, 1,3-benzodioxole, 1-benzothiophene, 1H-indazole, 1H-pyrrolo[2,3-b]pyridine, 1H-pyrrolo[2,3-c]pyridine, 1H-pyrrolo[3,2-b]pyridine, 1H-pyrrolo[3,2-c]pyridine, 2,1,3-benzoxadiazole, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine, 3H-imidazo[4,5-b]pyridine, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine, furo[2,3-c]pyridine, furo[3,2-b]pyridine, imidazo [1,2-a]pyridine, quinazoline, and thieno[3,2-c]pyridin-4(5H)-one, any of which is optionally substituted with 1 to 3 groups of R b .

9. The compound according to claim 1 , wherein R 1 is hydrogen;

X is hydrogen;

Y is phenyl optionally substituted with 1 to 3 groups of R a ;

A is B(OH) 2 , halo, or C 1-6 alkyl;

R 2 is selected from H and C 1-6 alkyl;

each R a is independently selected from C 1-6 alkyl, halogen, (CH 2 ) n CF 3 , OR 2 , (CHC 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, and O(CH 2 )nC 5-10 heterocyclyl, said alkyl, heterocyclyl and aryl are optionally substituted with 1 to 3 groups of R b ;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN;

n represents 0 to 5; and

provided that no more than one of said R a is (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl.

10. The compound according to claim 1 , wherein the compound is represented by structural formula II:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R 1 is NHCH 3 .

11. A compound according to claim 1 represented by structural formula VII:

wherein P represents pyridyl;

R1 is hydrogen;

each R 2 is independently selected from hydrogen and C 1-6 alkyl;

each R a is independently selected from C 1-6 alkyl, halogen, (CH 2 ) n CF 3 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 )nC 5-10 heterocyclyl, said alkyl, heterocyclyl and aryl are optionally substituted with 1 to 3 groups of R b ;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN; and

n represents 0 to 5.

12. A pharmaceutical composition comprising an inert carrier and an effective amount of a compound according to claim 1 .

13. A method of treating neurological and psychiatric disorders and diseases comprising administering to said patient a therapeutically effective amount of a compound according to formula I in claim 1 or a pharmaceutically acceptable salt thereof, said neurological and psychiatric disorders and diseases selected from schizophrenia, augmentation of effect of anti-psychotics in treatment of positive symptoms of schizophrenia, major depressive disorder, the depressive phase of bipolar disorder, substance dependency, ADD/ADHD, and cognitive deficit associated with said neurological and psychiatric disorders and diseases.

14. The composition according to claim 12 further comprising one or more therapeutically active compounds selected from the group consisting of opiate agonists or antagonists, calcium channel antagonists, 5HT, 5-HT˜A complete or partial receptor agonists or antagonists, sodium channel antagonists, N-methyl-D-aspartate (NMDA) receptor agonists or antagonists, COX-2 selective inhibitors, neurokinin receptor 1 (NKI) antagonists, non-steroidal anti-inflammatory drugs (NSAID), selective serotonin reuptake inhibitors (SSRI) and/or selective serotonin and norepinephrine reuptake inhibitors (SSNRI), tricyclic antidepressant drugs, norepinephrine modulators, lithium, valproate, norepinephrine reuptake inhibitors, monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase (RIMAs), alpha-adrenoreceptor antagonists, atypical anti-depressants, benzodiazepines, corticotropin releasing factor (CRF) antagonists, typical antipsychotics, atypical antipsychotics, neurontin (gabapentin) and pregabalin.

15. The compound of claim 1 or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof, wherein:

A represents hydrogen;

Y represents phenyl optionally substituted with 1 to 3 groups of R a ;

X represents hydrogen;

at least one of said 1 to 3 groups of R a represents indolyl, pyridyl, phenyl or indazolyl optionally substituted with 1 to 3 groups of R b ; and

each R b independently represents C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , C 3-6 cycloalkyl, (CH 2 ) n CF 3 , or CN.

16. The compound according to claim 15 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R 1 represents NH 2 .

17. The compound of claim 15 or a pharmaceutically acceptable salt, enantiomer, or and diastereomer thereof, wherein R 1 represents NHCH 3 .

18. The compound of claim 1 having the structure of formula II

or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof, wherein

R 1 represents —CH(OH)CH 2 -phenyl;

R 2 and R 3 are independently selected from H and C 1-6 alkyl;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN; and

n represents 0 to 5;

provided that no more than one of said R a is (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 )nC 5-10 heterocyclyl.

19. The compound according to claim 1 which is:

5-hydroxy-1-[3-(quinolin-5-yl)phenyl]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxybutyl)pyridin-4(1H)-one;

1-(3-bromophenyl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(3-cyclohex-1-en-1-ylphenyl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-thiophen-3-ylphenyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(1-hydroxy-2-phenylethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1H-indazol-4-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1-methyl-1H-indazol-6-yl)phenyl]pyridin-4(1H)-one;

1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(4′-chloro-3′-fluorobiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(3′-chlorobiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(2′-fluorobiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-pyridin-4-ylphenyl)pyridin-4(1H)-one;

1-[4′-chloro-3′-(trifluoromethyl)biphenyl-3-yl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(6-fluoropyridin-3-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(1-benzyl-1H-pyrazol-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(4′-morpholin-4-ylbiphenyl-3-yl)pyridin-4(1H)-one;

1-[3-(6-aminopyridin-3-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1H-pyrrolo[3,2-b]pyridin-6-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1H-indazol-4-yl)phenyl]pyridin-4(1H)-one;

1-[3-(3-chloropyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-methoxyphenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-fluorophenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1H-indazol-4-yl)-4-methoxyphenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-quinazolin-4-ylphenyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1,8-naphthyridin-4-yl)phenyl]pyridin-4(1H)-one;

1-[3-(5-fluoro-1-oxo-2,3-dihydro-1H-inden-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1H-indol-7-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1H-indazol-7-yl)phenyl]pyridin-4(1H)-one;

1-[3-(5-fluoro-1-methyl-1H-benzimidazol-7-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(9-methyl-9H-purin-6-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-quinolin-5-ylphenyl)pyridin-4(1H)-one;

1-[3-(1-benzothiophen-7-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-1-(3-isoquinolin-4-ylphenyl)-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(5-chloro-1H-pyrrolo[2,3 -b]pyridin-4-yl)phenyl]-5-hydroxy-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(5-methoxypyridin-3-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-isoquinolin-4 -ylphenyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(1-methyl-1H-indazol-4-yl)phenyl]pyrdin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(2-methyl-2H-indazol-4-yl)phenyl]pyrdin-4(1H)-one;

5-hydroxy-2-(2,2,2-trifluoro-1-hydroxyethyl)-1-{3[6-(trifluoromethyl)pyridin-2-yl]phenyl}pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(8-methylquinolin-5-yl)phenyl]pyridin-4(1H)-one;

1-[3-(2,1,3 -benzoxadiazol-4-yl)phenyl]-5-hydroxy-2-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-imidazo[1,2-a]pyridin-8-ylphenyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(6-methoxybiphenyl-3-yl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-isoquinolin-4 -yl-4 -methoxyphenyl)pyridin-4(1H)-one;

5-hydroxy-1[2-methyl-3-(1H-pyrrolo[2,3 -b]pyridin-5-yl)phenyl]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-1[2-methyl-3-(6-morpholin-4-ylpyridin-3-yl)phenyl]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one;

1-[4′-(1,3 -benzoxazol-2-ylamino)-2-methylbiphenyl-3-yl]-5-hydroxy-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one;

1-(5′-ethoxy-2′-fluoro-4,6-dimethoxybiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(2-methylbiphenyl-3-yl)pyridin-4(1H)-one;

5-hydroxy-2-phenyl-1-(3-quinolin-5-ylphenyl)pyridin-4(1H)-one;

1-(2′,3′-difluoro-2-methylbiphenyl-3-yl)-5-hydroxy-2 -hydroxyethyl)pyridin-4(1H)-one;

1-(5′-fluoro-2′-methoxy-6-methylbiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(2′,5′-difluoro-6-methylbiphenyl-3-yl)-5-hydroxy-2(1-hydroxyethyl)pyridin-4(1H)-one;

1-(3′-chloro-2′,6-dimethylbiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyrdin-4(1H)-one;

1-[5′-chloro-6-methyl-2′-(1-methylethoxy)biphenyl-3-yl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(6-methylbiphenyl-3-yl)pyridin-4(1H)-one;

1-(2′,5′-difluoro-6-methoxybiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(2′-chloro-5′,6-dimethoxybiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(6-methoxy-2′,3′-dimethylbiphenyl-3-yl)pyridin-4(1H)-one;

1-(5′-tert-butyl-2′,6-dimethoxybiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(2′-fluoro-5′,6-dimethoxybiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(2′-fluoro-6-methoxybiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[4-methoxy-3-(2-methylpyridin-4-yl)phenyl]pyridin-4(1H)-one;

1-[3-(5-fluoropyridin-3-yl)-4-methoxyphenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-[4,6-dimethoxy-2′-(trifluoromethyl)biphenyl-3-yl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-(5′-chloro-2′-fluoro-6-methoxybiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[6-methoxy-5′-methyl-2′-(1-methylethoxy)biphenyl-3-yl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[3-(6-hydroxypyridin-3-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-(3-thieno[2,3-b]pyridin-3-ylphenyl)pyridin-4(1H)-one;

1-(3′-cyclopropylbiphenyl-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(3-chloroquinolin-7-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

1-[3-(3-chloroisoquinolin-7-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxyethyl)-1-[4′-(pyridin-2-ylmethyl)biphenyl-3-yl]pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(2-hydroxy-2-pyrazolo[1,5-a]pyridin-7-ylethyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[2-hydroxy-2-(1,6-naphthyridin-8-yl)ethyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[2-hydroxy-2-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]pyridin-4(1H)-one;

5-hydroxy-2-[2-hydroxy-2-(6-methylpyridin-2-yl)ethyl]-1-(4′-methylbiphenyl-3-yl)pyridin-4(1H)-one;

1-[3-(6-fluoropyridin-3-yl)phenyl]-5-hydroxy-2-[2-hydroxy-2-(6-methylpyridin-2-yl)ethyl]pyridin-4(1H)-one;

5-hydroxy-2-[2-hydroxy-2-(6-methylpyridin-2-yl)ethyl]-1-[3-(1-methyl-1H-indol-5-yl)phenyl]pyridin-4(1H)-one;

1-[3′-(dimethylamino)biphenyl-3-yl]-5-hydroxy-2-[2-hydroxy-2-(6-methylpyridin-2-yl)ethyl]pyridin-4(1H)-one;

5-hydroxy-2-[2-hydroxy-2-(6-methylpyridin-2-yl)ethyl]-1-(3-[1,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)pyridin-4(1H)-one;

5-hydroxy-2-[2-hydroxy-2-(6-methylpyridin-2-yl)ethyl]-1-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-{2-hydroxy-2-[6-(trifluoromethyl)pyridin-3-yl]ethyl}pyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2-(6-chloropyridin-3-yl)-2-hydroxyethyl]-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[2-hydroxy-2-(3-methylpyridin-4-yl)ethyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[2-hydroxy-2-(5-methoxypyridin-3-yl)ethyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2-(6-ethoxypyridin-2-yl)-2-hydroxyethyl]-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(1-hydroxy-1-methylethyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(1-hydroxy-2-phenylethyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-3-bromo-5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one;

5-hydroxy-2-[hydroxy(phenyl)methyl]-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxy-2-methylpropyl)-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxy-2-phenylethyl)-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

20. A compound which is:

2-amino-1-(2′-cyclopropylbiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1H-indazol-4-yl)phenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[2′-(methoxymethyl)biphenyl-3-yl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(2-methylpyridin-3-yl)phenyl]pyridin-4(1H)-one;

2-amino-1-(2′-chloro-6′-fluorobiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-1-[3-(3-chloro-2-morpholin-4-ylpyridin-4-yl)phenyl]-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-(3-isoquinolin-5-ylphenyl)pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1-methyl-1H-indol-4-yl)phenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(7-methylimidazo[1,2-a]pyridin-6-yl)phenyl]pyridin-4(1H)-one;

2-amino-1-[3-(5-chloro-1H-pyrrolo[2,3 -b]pyridin-4-yl)phenyl]-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1-methyl-1H-indazol-4-yl)phenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1-methyl-1H-indazol-6-yl)phenyl]pyridin-4(1H)-one;

2-amino-1-[3-(6-fluoropyridin-3-yl)phenyl]-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-(3-pyridin-3-ylphenyl)pyridin-4(1H)-one;

2-amino-1-(2′,4′-difluorobiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

2-amino-1-[3-(6-aminopyridin-3-yl)phenyl]-5-hydroxypyridin-4(1H)-one;

2-amino-1-(3-{6-[3-(dimethylamino)propoxy]pyridin-3-yl}phenyl)-5-hydroxypyridin-4(1H)-one;

2-amino-1-[3-(2,2-difluoro-1,3-benzodioxol-4-yl)phenyl]-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1H-pyrrolo[3,2-b]pyridin-6-yl)phenyl]pyridin-4(1H)-one;

2-amino-1-[5-(1-benzyl-1H-pyrazol-4-yl)-2,4-dimethoxyphenyl]-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-(5-isoquinolin-5-yl-2,4-dimethoxyphenyl)pyridin-4(1H)-one;

2-amino-1-[4,6-dimethoxy-2′-(trifluoromethoxy)biphenyl-3-yl]-5-hydroxypyridin-4(1H)-one;

2-amino-1-{3-[6-(difluoromethyl)pyridin-2-yl]phenyl}-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-{3-[6-(2-hydroxy-1,1-dimethylethyl)pyridin-2-yl]phenyl}pyridin-4(1H)-one;

2-amino-5-hydroxy-1-{3-[6-(trifluoromethyl)-1 ,5-naphthyridin-2-yl]phenyl}pyridin-4(1H)-one;

2-[3-(2-amino-5-hydroxy-4-oxopyridin-1(4H)-yl)phenyl]pyridine-3-carbonitrile;

2-amino-5-hydroxy-1-[3-(6-methoxyquinolin-2-yl)phenyl]pyridin-4(1H)-one;

5′-(2-amino-5-hydroxy-4-oxopyridin-1(4H)-yl)-2-fluoro-2′-methoxybiphenyl-3-carbonitrile;

2-amino-1-(3′,5′-difluoro-2′-methoxy-2-methylbiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-1-(5′-ethoxy-2′-fluoro-2-methylbiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-[2-methyl-3-(1-methyl-1H-indazol-4-yl)phenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1H-indazol-5-yl)-2-methylphenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[2-methyl-3-(1-methyl-1H-indazol-5-yl)phenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[2-methyl-3-(1-methyl-1H-indazol-6-yl)phenyl]pyridin-4(1H)-one;

2-amino-1-(2′,3′-dichloro-6-methylbiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-1-(5′-chloro-2′-methoxy-6-methylbiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-1-(2′,5′-dichloro-6-methylbiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-1-(5′-ethoxy-2′-fluoro-6-methylbiphenyl-3-yl)-5-hydroxypyridin-4(1H)-one;

2-amino-5-hydroxy-1-(3-isoquinolin-5-yl-4-methylphenyl)pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[4-methyl-3-(2-methyl-2H-indazol-5-yl)phenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1H-indazol-6-yl)-4-methylphenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[3-(1H-indol-4-yl)-4-methylphenyl]pyridin-4(1H)-one;

2-amino-5-hydroxy-1-[4-methyl-3-(8-methylquinolin-5-yl)phenyl]pyridin-4(1H)-one;

2-amino-1-[3-(2-chloro-5-methylphenoxy)-4-methylphenyl]-5-hydroxypyridin-4(1H)-one;

N-{1-[5-hydroxy-1-(3-isoquinolin-4-ylphenyl)-4-oxo-1,4-dihydropyridin-2-yl]ethyl}methanesulfonamide;

2-[1-(dimethylamino)ethyl]-5-hydroxy-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

2-(1-aminoethyl)-5-hydroxy-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(pyridin-2-ylamino)pyridin-4(1H)-one;

1-(Biphenyl-3-yl)-5-hydroxy-2-(methylamino)pyridin-4(1H)-one(4);

2-Amino-1-(biphenyl-3-yl)-5-hydroxypyridin-4(1H)-one(3);

or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

21. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

at least one of said 1 to 3 groups of R a is selected from C 6-10 aryl and C 5-10 heterocyclyl, wherein said aryl and heterocyclyl are optionally substituted with 1 to 3 groups of R b .

22. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein at least one of said 1 to 3 groups of R a is C 6-10 aryl optionally substituted with 1 to 3 groups of R b .

23. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein at least one of said 1 to 3 groups of R a is phenyl optionally substituted with 1 to 3 groups of R b .

24. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein at least one of said 1 to 3 groups of R a is phenyl substituted with 1 to 3 groups of R b .

25. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein at least one of said 1 to 3 groups of R a is phenyl.

26. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein at least one of said 1 to 3 groups of R a is C 5-10 heterocyclyl optionally substituted with 1 to 3 groups of R b .

27. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein at least one of said 1 to 3 groups of R a is 1,3-benzodioxole optionally substituted with 1 to 3 groups of R b .

28. The compound according to claim 7 , 9 , 10 , or 11 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein at least one of said 1 to 3 groups of R a is 1H-pyrrolo[2,3-b]pyridine optionally substituted with 1 to 3 groups of R b .

29. A compound which is 1-biphenyl-3-yl-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

30. A compound which is 1-biphenyl-3-yl-5-hydroxy-2-(1-hydroxy-2-phenylethyl)pyridin-4(1H)-one or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

31. A compound which is 1-(biphenyl-3-yl)-5-hydroxy-2-(methylamino)pyridin-4(1H)-one or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

32. A compound which is 2-amino-1-(biphenyl-3-yl)-5-hydroxypyridin-4(1H)-one or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

33. A compound which is 1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)-pyridin-4(1H)-one or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

34. A compound represented by structural formula I:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

R 1 is C 1-10 alkyl optionally substituted with 1 to 3 groups independently selected from halo, OH, O—C 1-6 alkyl, NR 2 R 3 , CF 3 , C 6-10 aryl, C 5-10 heterocyclyl, C 6-10 aryl, and cyano; provided that R 1 contains no more than one aryl or heterocyclyl;

R 2 and R 3 are independently selected from H, OH, C 1-6 alkyl and N(CH 3 ) 2 ;

A and X are each hydrogen;

Y is phenyl substituted with 1 to 3 groups of R a ;

each R a is independently selected from C 1-6 alkyl, halogen, (CH 2 ) n CF 3 , OR 2 , (CH 2 ) n 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, and O(CH 2 ) n C 5-10 heterocyclyl, said alkyl, heterocyclyl and aryl are optionally substituted with 1 to 3 groups of R b ; provided that at least one of said R a on Y is aryl or heterocyclyl optionally substituted with 1 to 3 groups of R b and no more than one of said R a is (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 )nC 5-10 heterocyclyl;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN; and

n represents 0 to 5.

35. The compound according to claim 34 , wherein

R 1 is C 1-10 alkyl optionally substituted with 1 to 3 groups selected from OH and CF 3 .

36. The compound according to claim 34 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

R a is selected from C 6-10 aryl and C 5-10 heterocyclyl, and said aryl and heterocyclyl are optionally substituted with 1 to 3 groups of R b ; and

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN.

37. The compound according to claim 34 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R a is selected from naphthyridine, indolyl, benzodioxaolyl, pyridyl, furopyridinyl, isoindolyl, pyridooxazinyl, pyrrolopyridinyl, quinoxalinyl, quinazolinyl, quinolinyl, isoquinolinyl, phenyl, indazolyl, [1,2,4]triazolo[1,5-a]pyridine, 1,2,3,4-tetrahydroisoquinoline, 1,3-benzodioxole, 1-benzothiophene, 1H-indazole, 1H-pyrrolo[2,3-b]pyridine, 1H-pyrrolo[2,3-c]pyridine, 1H-pyrrolo[3,2-b]pyridine, 1H-pyrrolo[3,2-c]pyridine, 2,1,3-benzoxadiazole, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine, 3H-imidazo[4,5-b]pyridine, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine, furo[2,3-c]pyridine, furo[3,2-b]pyridine, imidazo[1,2-a]pyridinen, quinazoline, and thieno[3,2-c]pyridin-4(5H)-one, any of which is optionally substituted with 1 to 3 groups of R b .

38. A compound represented by structural formula I:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

R 1 is C 1-10 alkyl optionally substituted with 1 to 3 groups independently selected from halo, OH, O—C 1-6 alkyl, NR 2 R 3 , CF 3 , C 6-10 aryl, C 5-10 heterocyclyl, OC 6-10 aryl, and cyano; provided that R 1 contains no more than one aryl or heterocyclyl;

R 2 and R 3 are independently selected from H, OH, C 1-6 alkyl and N(CH 3 ) 2 ;

A and X are each hydrogen;

Y is phenyl substituted with 1 to 3 groups of R a ;

R a is is C 6-10 aryl optionally substituted with 1 to 3 groups of R b ;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , —O—, N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN; and

n represents 0 to 5.

39. The compound according to claim 38 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R a is phenyl optionally substituted with 1 to 3 groups of R b .

40. The compound according to claim 38 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R a is phenyl.

41. A compound represented by structural formula I:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

R 2 and R 3 are independently selected from H, OH, C 1-6 alkyl and N(CH 3 ) 2 ;

A and X are each hydrogen;

Y is phenyl substituted with 1 to 3 groups of R a ;

R a is is C 5-10 heterocyclyl optionally substituted with 1 to 3 groups of R b ;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , —O—, N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 CF 3 , and CN; and

n represents 0 to 5.

42. The compound according to claim 41 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R a is 1,3-benzodioxole optionally substituted with 1 to 3 groups of R b .

43. The compound according to claim 41 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R a is 1H-pyrrolo[2,3-b]pyridine optionally substituted with 1 to 3 groups of R b .

44. A compound represented by structural formula II:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

R 1 is NR 2 R 3 ;

R 2 and R 3 are independently selected from H and C 1-6 alkyl;

each R b is independently selected from C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , and CN; and

n represents 0 to 5;

provided that no more than one of said R a is (CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl.

45. The compound according to claim 44 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein each of R 2 and R 3 is H.

46. The compound according to claim 44 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein each of R 2 and R 3 is C 1-6 alkyl.

47. The compound according to claim 44 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R a is (CH 2 ) n C 6-10 aryl optionally substituted with 1 to 3 groups of R b .

48. The compound according to claim 44 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein R a is phenyl.

49. A compound of structural formula I:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

A represents B(OH) 2 , NO 2 , halo, OH, C(O)NH(CH 2 ) n C(O)N(R 3 ) 2 , C 3-10 cycloalkyl, or C 1-6 alkyl;

X represents hydrogen;

Y represents phenyl or pyridyl, any of which is optionally substituted with 1 to 3 groups of R a ;

R 1 represents hydrogen;

R 2 and R 3 are independently selected from H, OH, C 1-6 alkyl and N(CH 3 ) 2 ;

each R a independently represents C 1-6 alkyl, halogen, hydroxyl, (CH 2 ) n CF 3 , OCHF 2 , OCF 3 , C 3-6 cycloalkyl, O(CH 2 ) n C 3-6 cycloalkyl, NR 2 C(O)R 2 , C(O)N(R 2 ) 2 , C(R 2 ) 2 OR 2 , C(O)R 2 , NO 2 , CN, N(R 2 ) 2 , (CH 2 ) n C(O)OR 2 , SO 2 R 2 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, NH(CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5 - 10 heterocyclyl, said cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of R b ;

each R b independently represents C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , or CN; and

n represents 0 to 5; and

provided that no more than one of said R a of Y is cycloalkyl, heterocyclyl or aryl.

50. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein Y is phenyl optionally substituted with 1 to 3 groups of R a .

51. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein Y is phenyl substituted with R a .

52. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

Y is phenyl substituted with R a ; and

R a is phenyl.

53. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein X is hydrogen; and A is C 1-6 alkyl.

54. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

X is hydrogen; and

A is B(OH) 2 .

55. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

X is hydrogen;

A is B(OH) 2 ; and

Y is phenyl optionally substituted with 1 to 3 groups of R a .

56. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

X is hydrogen; and

A is OH.

57. The compound according to claim 49 or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

X is hydrogen;

A is OH; and

Y is pyridyl optionally substituted with 1 to 3 groups of R a .

58. A compound which is:

5-hydroxy-2-(hydroxymethyl)-1-(4-morpholin-4 -ylphenyl)pyridin-4(1H)-one ;

1-(3,5-dimethylphenyl)-5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one;

5-hydroxy-2-(hydroxymethyl)-1-(3-methoxyphenyl)pyridin-4(1H)-one ;

1-[3-(dimethylamino)phenyl]-5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one

or a pharmaceutically acceptable salts, enantiomers, or diastereomers thereof.

59. A compound which is:

3-hydroxy-1-phenylpyridin-4(1H)-one;

1-biphenyl-4-yl-3-hydroxypyridin-4(1H)-one;

1-(4-butylphenyl)-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-[4-(trifluoromethyl)phenyl]pyridin-4(1H)-one;

1-[4-chloro-3-(trifluoromethyl)phenyl]-3-hydroxypyridin-4(1H)-one;

1-(2,4-dichlorophenyl)-3-hydroxypyridin-4(1H)-one;

1-(3,5-dichlorophenyl)-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-(3-phenoxyphenyl)pyridin-4(1H)-one;

1-(3-chlorophenyl)-3-hydroxypyridin-4(1H)-one;

1-(2-fluoro-5-methoxyphenyl)-3-hydroxypyridin-4(1H)-one;

1-{3-chloro-4-[(4-chlorophenyl)carbonyl]phenyl}-3-hydroxypyridin-4(1H)-one;

1-(3-fluoro-5-methoxyphenyl)-3-hydroxypyridin-4(1H)-one;

1-[3-butoxy-5-(trifluoromethyl)phenyl]-3-hydroxypyridin-4(1H)-one;

1-(3-bromo-5-fluoro-4-methylphenyl)-3-hydroxypyridin-4(1H)-one;

2′-fluoro-5′-(3-hydroxy-4-oxopyridin-1(4H)-yl)-4-(trifluoromethyl)biphenyl-2-carbonitrile;

1-[4-(3-chlorophenoxy)-3-(trifluoromethyl)phenyl]-3-hydroxypyridin-4(1H)-one;

N-[2-chloro-4-(3-hydroxy-4-oxopyridin-1(4H)-phenyl]pentanamide;

1-[3-fluoro-5-(pyridin-3-yloxy)phenyl]-3-hydroxypyridin-4(1H)-one;

1-[3-(6-fluoropyridin-3-yl)phenyl]-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]pyridin-4(1H)-one;

3-hydroxy-1-(3-pyridin-4-ylphenyl)pyridin-4(1H)-one;

3-hydroxy-1-{3-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}pyridin-4(1H)-one;

1-[3-bromo-4-(trifluoromethoxy)phenyl]-3-hydroxypyridin-4(1H)-one;

1-(4-ethoxypheny 1)-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-[4-methoxy-3-(1-methylethyl)phenyl]pyridin-4(1H)-one;

3-hydroxy-1-[4-(3-pyridin-4-ylpropoxy)phenyl]pyridin-4(1H)-one;

3-hydroxy-1-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-4(1H)-one;

1-[3-chloro-4-(diethylamino)phenyl]-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-(4-{[4-(hydroxymethyl)cyclohexyl]methoxy}phenyl)pyridin-4(1H)-one;

1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-[4-(4-pyridin-4-ylpiperazin-1-yl)phenyl]pyridin-4(1H)-one ;

1-[4-(dimethylamino)phenyl]-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-{4-[3-pyridin-3-yl-5-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}pyridin-4(1H)-one;

1-[4-(cyclopentyloxy)phenyl]-3-hydroxypyridin-4(111)-one;

3-hydroxy-1-(4-morpholin-4-ylphenyl)pyridin-4(1H)-one;

3-hydroxy-1-[4-(4-methoxyphenoxy)phenyl]pyridin-4(1H)-one;

3-hydroxy-1-[4-(1H-pyrazol-1-yl)phenyl]pyridin-4(1H)-one;

1-{3-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-[3-(1H-pyrrolo[3,2-b]pyridin-6-yl)phenyl]pyridin-4(1H)-one;

1-(6-chlorobiphenyl-3-yl)-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-[3-(1H-indazol-4-yl)phenyl]pyridin-4(1H)-one;

3-hydroxy-1-(4′-pyridin-2-ylbiphenyl-3-yl)pyridin-4(1H)-one;

1-[3-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)phenyl]-3-hydroxypyridin-4(1H)-one;

3-hydroxy-1-(3-isoquinolin-4-yl)phenyl)pyridin-4(1H)-one;

5-(3-hydroxy-4-oxopyridin-1(4H)-yl)biphenyl-3-carboxylic acid;

3-hydroxy-6′-phenyl-4H-1,2′-bipyridin-4-one;

3-hydroxy-4′-phenyl-4H-1,2′-bipyridin-4-one;

3-hydroxy-6′-quinolin-5-yl-4H-1,2′-bipyridin-4-one;

6′-(8-fluoro-2-methylquinolin-7-yl)-3-hydroxy-4H-1,2′-bipyridin-4-one;

6′-biphenyl-3-yl-3-hydroxy-4H-1,2′-bipyridin-4-one;

3-hydroxy-3′-phenyl-4H-1,2′-bipyridin-4-one;

4′-(4-tert-butylphenyl)-3-hydroxy-4H-1,2′-bipyridin-4-one;

4′-(3,4-dichlorophenyl)-3-hydroxy-4H-1,2′-bipyridin-4-one;

3-hydroxy-4′[4-(2-methylpropyl)phenyl]-4H-1,2′-bippidin-4-one;

4′[2-fluoro-4-(trifluoromethyl)phenyl]-3-hydroxy-4H-1,2′-bipyridin-4-one;

3-hydroxy-4′[1-(2-methylpropyl)-1H-pyrazol-4-yl]-4H-1,2′-bipyridin-4-one;

3-hydroxy-4′-quinolin-5-yl-4H-1,2′-bipyridin-4-one;

4′[4-(difluoromethoxy)phenyl]-3-hydroxy-4H-1,2′-bipyridin-4-one;

4′-(5-chloro-1H-pyrrolo[2,3-b)]pyridin-4-yl)-3-hydroxy-4H-1,2′-bipyridin-4-one;

3″-fluoro-3-hydroxy-4H-1,2′:4′,4″-terpyridin-4-one;

3-hydroxy-6″-(trifluoromethyl)-4H-1,2′:4′,2″-terpyridin-4-one;

4′-(2-tert-butyl-1,3-thiazol-4-yl)-3-hydroxy-4H-1,2′-bipyridin-4-one;

3-hydroxy-6″-(4-methylpiperazin-1-yl)-4H-1,2′:4′,2 ″-terpyridin-4-one;

3-hydroxy-6″-(2-methyl-1H-imidazol-1-yl)-4H-1,2′:4′,2″-terpyridin-4-one;

4′-(4-cyclopropylphenyl)-3′-fluoro-3-hydroxy-4H-1,2′-bipyridin-4-one;

3′-fluoro-3-hydroxy-4′-(1,2,3,4-tetrahydroisoquinolin-6-yl)-4H-1,2′-bipyridin-4-one;

3′-fluoro-3-hydroxy-4′-quinolin-5-yl-4H-1,2′-bipyridin-4-one;

3′-fluoro-3-hydroxy-4′[1,2,4]triazolo[1,5-a]pyridin-7-yl-4H-1,2′-bipyridin-4-one;

3′-fluoro-3-hydroxy-4′-(1H-pyrrolo[2,3-b]pyridin-5-yl)-4H-1,2′-bipyridin-4-one;

3′-fluoro-3-hydroxy-4′-(1-methyl-1H-indazol-6-yl)-4H-1,2′-bipyridin-4-one ;

3′-fluoro-3-hydroxy-4′-(3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)-4H-1,2′-bipyridin-4-one; 3′-fluoro-3-hydroxy-4′-phenyl-4H-1,2′-bipyridin-4-one;

3′-fluoro-3-hydroxy-4′-imidazo[1,2-a]pyridin-6-yl-4H-1,2′-bipyridin-4-one;

4′-(4-chloro-3-fluorophenyl)-3′-fluoro-3-hydroxy-4H- ,2′-bipyridin-4-one;

or a pharmaceutically acceptable salts, and individual enantiomer& or vend diastereomer & thereof.

60. A compound which is:

1-biphenyl-3-yl-2-[2-(2,3-dihydro-1,4-benzodioxin-2-yl)ethyl]-5-hydroxypylidin-4(1H)-one;

1-biphenyl-3-yl-2-(2-biphenyl-2-yl-2-hydroxyethyl)-5-hydroxypyridin-4(1H)-one;

2-[cyclohexyl(hydroxy)methyl]-5-hydroxy-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-2-(cyclopentylmethyl)-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-(2-cyclopropylethyl)-5-hydroxypyridin-4(1H)-one;

2-[cyclopropyl(hydroxy)methyl]-5-hydroxy-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-1-methylethyl]-5-hydroxypyridin-4(1H)-one;

3-(1-biphenyl-3-yl-5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)-N,N-diethylpropanamide;

1-biphenyl-3-yl-2-(difluoromethyl)-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-(dimethylamino)-5-hydroxypyridin-4(1H)-one ;

5-hydroxy-2-(2-hydroxy-1,3-dimethylbutyl)-1-phenylpyridin-4(1H)-one;

1-biphenyl-3-yl-2-(fluoromethyl)-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-N-3-(dimethylamino)-3-oxopropyl]-5-hydroxy-4-oxo-1,4-dihydropyridine-3-carboxamide;

2-[(1-biphenyl-3-yl-5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl]isoquinolin-3(2H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(methoxymethyl)pyridin-4(1H)-one;

5-hydroxy-2-methyl-1-[3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-1-[3-(2-methoxypyridin-3-yl)phenyl]-2-methylpyridin-4(1H)-one;

5-hydroxy-1-[3-(1H-indol-5-yl)phenyl]-2-methylpyridin-4(1H)-one;

N-[4′-(5-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)biphenyl-2-yl]-4-methylbenzenesulfonamide;

5-hydroxy-1-{4′-[(4-hydroxypiperidin-1-yl)carbonyl]biphenyl-4-yl}-2-methylpyridin-4(1H)-one;

4′-(5-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)-4-methylbiphenyl-2-carbonitrile;

1-[3′-(1,1-dioxidothiomorpholin-4-yl)biphenyl-4-yl]-5-hydroxy-2-methylpyridin-4(1H)-one;

5-hydroxy-1-[3′-(3-hydroxypropyl)biphenyl-4-yl]-2-methylpyridin-4(1H)-one;

1-[4-(4-fluorobenzyl)phenyl]-5-hydroxy-2-methylpyridin-4(1H)-one;

1-[2′-(difluoromethoxy)biphenyl-4-yl]-5-hydroxy-2-methylpyridin-4(1H)-one;

5-hydroxy-2-methyl-1(3-[1,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)pyridin-4(1H)-one;

4-[3-(5-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)phenyl]-2,3-dihydro-1H-isoindol-1-one;

5-hydroxy-1-{3-[2-(hydroxymethyl)pyridin-4-yl[phenyl}-2-methylpyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-methylpyridin-4(1H)-one;

5-hydroxy-2-methyl-4′-phenyl-414-1,2′-bipyridin-4-one;

1-biphenyl-3-yl-5-hydroxy-2-(1-methylethyl)pyridin-4(1H)-one;

1-(2′-fluorobiphenyl-3-yl)-5-hydroxy-2-(1-methylethyppyridin-4(1H)-one;

5-hydroxy-2-(1-methylethyl)-1-(3-pyridin-3-ylphenyl)pyridin-4(1H)-one;

1-[3-(6-fluoropyridin-3-yl)phenyl]-5-hydroxy-2-(1-methylethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-methylethyl)-1-[3-(1-methyl-1H-indol-5-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-methylethyl)-1-[3-(1-propyl-1H-pyrazol-4-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-methylethyl)-1-[3-(1H-pyrrolo[3,2-b]pyridin-6-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-2-(1-methylethyl)-1-{3-[2-(trifluoromethyl)pyridin-4-yl]phenyl}pyridin-4(1H)-one;

5-hydroxy-2-(1-methylethyl)-1-[3-(3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)phenyl]pyridin-4(1H)-one;

5-hydroxy-1-(3-imidazo[1,2-a]pyridin-6-ylphenyl)-2-(1-methylethyl)pyridin-4(1H)-one;

1-[3-(2-fluoropyridin-4-yl)phenyl]-5-hydroxy-2-methylethyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2-(4-tert-butylphenyl)-1-methylethyl]-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(2-methylpropyl)pyridin-4(1H)-one;

5-hydroxy-1-(3-isoquinolin-4-ylphenyl)-2-[1-(methylsulflnyL)ethyl]pyrudin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-morpholin-4-ylpyridin-4(1H)-one;

5-hydroxy-2-phenyl-1-(3-quinolin-5-ylphenyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-2-{1,1-dimethyl-2-[3-(trifluoromethyl)phenyl]ethyl}-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[(E)-2-phenylethenyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-2-{2-[3-fluoro-4-(trifluoromethyl)phenyll ethyl}-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2-(2-fluorophenyl)-2-hydroxyethyl]-5-hydroxypyridin-4(1H)-one;

3-[2-(1-biphenyl-3-yl-5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)- -hydroxyethyl]benzonitrile;

1-biphenyl-3-yl-5-hydroxy-2-[2-hydroxy-2-(3-methoxyphenyl)ethyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2-(4-tert-butylphenyl)-2-hydroxyethyl]-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-{2-[3-fluoro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2(3,4-difluorophenyl)-1-hydroxyethyl]-5-hydroxypyridin-4(1H)-one;

5-hydroxy-2-(1-hydroxy-2-phenylethyl)-1-phenylpyridin-4(1H)-one;

2-[2-(3,4-difluorophenyl)-1-hydroxyethyl]-5-hydroxy-1-phenylpyridin-4(1H)-one;

5-hydroxy-2-[1-hydroxy-2-(2-methylphenyl)ethyl]-1-phenylpyridin-4(1H)-one;

3-[2-hydroxy-2-(5-hydroxy-4-oxo-1-phenyl-1,4-dihydropridin-2-yl)ethyl]benzonitrile;

1-biphenyl-3-yl-2-[(3,4-difluorophenyl)(hydroxy)methyl]-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-[(4-chloro-3-fluorophenyl)(hydroxy)methyl]-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-[(4-fluorophenyl)(hydroxy)methyl]-5-hydroxypyridin-4(1H)-one;

5-hydroxy-2-[hydroxy(3-methylphenyL)methyl]-1-phenylpyridin-4(1H)-one;

5-hydroxy-2-[hydroxy(3-methoxyphenyL)methyl]-1-phenylpyridin-4(1H)-one;

5-hydroxy-2-(2-hydroxy-1-methyl-4-phenylbutyl)-1-phenylpyridin-4(1H)-one;

5-hydroxy-2-(1-methyl-2-phenylethyl)-1-phenylpyridin-4(1H)-one;

1-biphenyl-3-yl-2-{2-[4-chloro-3-(trifluoromethyl)phenyl]-1-methylethyl}-5-hydroxypyridin-4(1H)-one;

2-[2-(2,3-difluorophenyl)-1-methylethyl]-5-hydroxy-1-phenylpyridin-4(1H)-one;

2-[2-(3-fluorophenyl)-1-methylethyl]-5-hydroxy-1-phenylpyridin-4(1H)-one;

2-[2-(3,5-dimethylphenyl)-1-methylethyl]-5-hydroxy-1-phenylpyridin-4(1H)-one;

2-(2-cyclohexyl-1-methylethyl)-5-hydroxy-1-phenylpyridin-4(1H)-one;

5-hydroxy-2-[2-hydroxy-2-(3-methoxyphenyl)-1-methylethyl]-1-phenylpyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[2-(5-phenyl-1,2,4-oxadiazol-3-yl)ethyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-2-{2-[2-(2-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]-1-methylethyl}-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[2-hydroxy-2-(2-methoxypyrimidin-5-yl)ethyl]pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-[2-hydroxy-2-(1,3-thiazol-4-yl)ethylfpyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(trimethylsilyl)pyridine-4(1H)-one;

or a pharmaceutically acceptable salts, and-individual enantiomers, or and diastereomers thereof.

61. A pharmaceutical composition comprising an inert carrier and an effective amount of a compound according to claim 11 .

62. The composition according to claim 61 further comprising one or more therapeutically active compounds selected from the group consisting of opiate agonists or antagonists, calcium channel antagonists, 5HT, 5-HT 1A complete or partial receptor agonists or antagonists, sodium channel antagonists, N-methyl-D-aspartate (NMDA) receptor agonists or antagonists, COX-2 selective inhibitors, neurokinin receptor 1 (NKI) antagonists, non-steroidal anti-inflammatory drugs (NSAID), selective serotonin reuptake inhibitors (SSRI) and/or selective serotonin and norepinephrine reuptake inhibitors (SSNRI), tricyclic antidepressant drugs, norepinephrine modulators, lithium, valproate, norepinephrine reuptake inhibitors, monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase (RIMAs), alpha-adrenoreceptor antagonists, atypical anti-depressants, benzodiazepines, corticotropin releasing factor (CRF) antagonists, neurontin (gabapentin) and pregabalin.

63. A pharmaceutical composition comprising an inert carrier and an effective amount of a compound according to claim 34 .

64. The composition according to claim 12 or 63 further comprising one or more therapeutically active compounds selected from the group consisting of opiate agonists or antagonists, calcium channel antagonists, 5HT, 5-HT 1A complete or partial receptor agonists or antagonists, sodium channel antagonists, N-methyl-D-aspartate (NMDA) receptor agonists or antagonists, COX-2 selective inhibitors, neurokinin receptor 1 (NKI) antagonists, non-steroidal anti-inflammatory drugs (NSAID), selective serotonin reuptake inhibitors (SSRI) and/or selective serotonin and norepinephrine reuptake inhibitors (SSNRI), tricyclic antidepressant drugs, norepinephrine modulators, lithium, valproate, norepinephrine reuptake inhibitors, monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase (RIMAs), alpha-adrenoreceptor antagonists, atypical anti-depressants, benzodiazepines, corticotropin releasing factor (CRF) antagonists, neurontin (gabapentin) and pregabalin.

65. A pharmaceutical composition comprising an inert carrier and an effective amount of a compound according to claim 44 .

66. The composition according to claim 65 further comprising one or more therapeutically active compounds selected from the group consisting of opiate agonists or antagonists, calcium channel antagonists, 5HT, 5-HT 1A complete or partial receptor agonists or antagonists, sodium channel antagonists, N-methyl-D-aspartate (NMDA) receptor agonists or antagonists, COX-2 selective inhibitors, neurokinin receptor 1 (NKI) antagonists, non-steroidal anti-inflammatory drugs (NSAID), selective serotonin reuptake inhibitors (SSRI) and/or selective serotonin and norepinephrine reuptake inhibitors (SSNRI), tricyclic antidepressant drugs, norepinephrine modulators, lithium, valproate, norepinephrine reuptake inhibitors, monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase (RIMAs), alpha-adrenoreceptor antagonists, atypical anti-depressants, benzodiazepines, corticotropin releasing factor (CRF) antagonists, neurontin (gabapentin) and pregabalin.

67. A pharmaceutical composition comprising an inert carrier and an effective amount of a compound according to claim 49 .

68. The composition according to claim 67 further comprising one or more therapeutically active compounds selected from the group consisting of opiate agonists or antagonists, calcium channel antagonists, 5HT, 5-HT 1A complete or partial receptor agonists or antagonists, sodium channel antagonists, N-methyl-D-aspartate (NMDA) receptor agonists or antagonists, COX-2 selective inhibitors, neurokinin receptor 1 (NKI) antagonists, non-steroidal anti-inflammatory drugs (NSAID), selective serotonin reuptake inhibitors (SSRI) and/or selective serotonin and norepinephrine reuptake inhibitors (SSNRI), tricyclic antidepressant drugs, norepinephrine modulators, lithium, valproate, norepinephrine reuptake inhibitors, monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase (RIMAs), alpha-adrenoreceptor antagonists, atypical anti-depressants, benzodiazepines, corticotropin releasing factor (CRF) antagonists, neurontin (gabapentin) and pregabalin.

69. A compound of structural formula I:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

A represents hydrogen, B(OH) 2 , halo, OH, C 3-10 cycloalkyl, or C 1-6 alkyl;

X represents hydrogen or C 1-6 alkyl;

Y represents benzimidazolyl, benzthiazolyl, benzoxazolyl, benzpiperidinyl, quinolyl, indolyl, tetrahydroquinoline, indazolyl, or pyridyl, any of which is optionally substituted with 1 to 3 groups of R a , provided that no more than one of said R a is cycloalkyl, heterocyclyl or aryl;

R 1 represents hydrogen, NR 2 R 3 or C 1-10 alkyl, said alkyl optionally substituted with 1 to 3 groups of C 3-6 cycloalkyl, halo, OH, CF 3 , OR 2 , NR 2 R 3 , cyano, C 6-10 aryl, and C 5-10 heterocyclyl, wherein said aryl and heterocyclyl optionally substituted with 1 to 3 groups of C 1-6 alkyl, halogen, hydroxyl, CF 3 , OCF 3 , OCHF 2 , CN, OR 2 , NR 2 R 3 ;

each of R 2 and R 3 independently represent H, OH, C 1-6 alkyl and N(CH 3 ) 2 ;

each R a independently represents C 1-6 alkyl, halogen, hydroxyl, CF 3 , OCHF 2 , OCF 3 , C 3-6 cycloalkyl, O(CH 2 ) n C 3-6 cycloalkyl, NR 2 C(O)R 2 NR 2 C(O)R 2 , C(O)N(R 2 ) 2 , C(R 2 ) 2 OR 2 , C(O)R 2 , NO 2 , CN, N(R 2 ) 2 , SO 2 R 2 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, NH(CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl, said cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of R b ;

each R b independently represents C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , S(O) 2 NR 2 R 3 , (CH 2 ) n C 6-10 aryl, (CH 2 ) n heterocyclyl, C(O)(CH 2 ) n heterocyclyl, NH(CH 2 ) n heterocyclyl, C(O)NHC 3-6 cycloalkyl, CH 2 OH, CF 3 , —O—, OR 2 , C 3-6 cycloalkyl, or CN; and

n represents 0 to 5.

70. The compound of claim 69 , wherein

A represents hydrogen;

X represents hydrogen;

Y represents pyridyl or benzimidazolyl, any of which optionally substituted with 1 to 3 groups of R a ; and

R 1 represents C 1-10 alkyl, said alkyl optionally substituted with 1 to 3 groups of C 3-6 cycloalkyl, halo, OH, CF 3 , OR 2 , NR 2 R 3 , cyano, C 6-10 aryl, and heterocyclyl, wherein said aryl and heterocyclyl optionally substituted with 1 to 3 groups of C 1-6 alkyl, halogen, hydroxyl, CF 3 , OCF 3 , OCHF 2 , CN, OR 2 , NR 2 R 3 .

71. The compound of claim 69 , wherein

A represents hydrogen;

X represents hydrogen;

Y represents pyridyl or benzimidazolyl, any of which optionally substituted with 1 to 3 groups of R a ;

R 1 represents hydrogen or C 1-10 alkyl; and

each R a independently represents C 1-6 alkyl, halogen, hydroxyl, (CH 2 ) n CF 3 , OCHF 2 , OCF 3 , C 3-6 cycloalkyl, O(CH 2 ) n C 3-6 cycloalkyl, NR 2 C(O)R 2 , C(O)N(R 2 ) 2 , C(R 2 ) 2 OR 2 , C(O)R 2 , NO 2 , CN, N(R 2 ) 2 , (CH 2 ) n C(O)OR 2 , SO 2 R 2 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, NH(CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl, said cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of R b ; and

each R b independently represents C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , or CN.

72. The compound of claim 71 , wherein

A, X, and R 1 each represent hydrogen;

Y represents pyridyl or benzimidazolyl, any of which optionally substituted with 1 to 3 groups of R a , provided that at least one of said R a is selected from (CH 2 ) n C 6-10 aryl, or (CH 2 ) n C 5-10 heterocyclyl.

73. A compound of structural formula I:

or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, wherein:

A represents hydrogen, B(OH) 2 , halo, OH, C 3-10 cycloalkyl, or C 1-6 alkyl;

X represents hydrogen or C 1-6 alkyl;

Y represents phenyl optionally substituted with 1 to 3 groups of R a , wherein at least one of said 1 to 3 groups of R a represents hydroxyl, CF 3 , OCHF 2 , OCF 3 , C 3-6 cycloalkyl, O(CH 2 ) n C 3-6 cycloalkyl, NR 2 C(O)R 2 NR 2 C(O)R 2 , C(O)N(R 2 ) 2 , C(R 2 ) 2 OR 2 , C(O)R 2 , NO 2 , CN, N(R 2 ) 2 , SO 2 R 2 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, NH(CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl, said cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of R b , provided that no more than one of said R a is cycloalkyl, heterocyclyl or aryl;

R 1 represents NR 2 R 3 or C 1-10 alkyl, said alkyl optionally substituted with 1 to 3 groups of C 3-6 cycloalkyl, halo, OH, CF 3 , OR 2 , NR 2 R 3 , cyano, C 6-10 aryl, and heterocyclyl, wherein said aryl and heterocyclyl optionally substituted with 1 to 3 groups of C 1-6 alkyl, halogen, hydroxyl, CF 3 , OCF 3 , OCHF 2 , CN, OR 2 , and NR 2 R 3 ;

each of R 2 and R 3 independently represent H, OH, or C 1-6 alkyl;

(CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl, said cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of R b ;

each R b independently represents C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , or CN; and

n represents 0 to 5.

74. The compound of claim 73 , wherein:

A and X each represents hydrogen;

Y represents phenyl optionally substituted with 1 to 3 groups of R a , wherein at least one of said 1 to 3 groups of R a is selected from (CH 2 ) n C 5-10 heterocyclyl and (CH 2 ) n C 6-10 aryl, said aryl and heterocyclyl optionally substituted with 1 to 3 groups of R b ; and

R 1 represents C 1-10 alkyl, said alkyl optionally substituted with 1 to 3 groups of C 3-6 cycloalkyl, halo, OH, CF 3 , OR 2 , NR 2 R 3 , cyano, C 6-10 aryl, and C 5-10 heterocyclyl, wherein said aryl and heterocyclyl optionally substituted with 1 to 3 groups of C 1-6 alkyl, halogen, hydroxyl, CF 3 , OCF 3 , OCHF 2 , CN, OR 2 , and NR 2 R 3 .

75. The compound of claim 73 , wherein:

A and X each represents hydrogen;

Y represents phenyl optionally substituted with 1 to 3 groups of Ra, wherein at least one of said 1 to 3 groups of R a is selected from (CH 2 ) n C 5-10 heterocyclyl and (CH 2 ) n C 6-10 aryl, said aryl and heterocyclyl optionally substituted with 1 to 3 groups of R b ; and

R 1 represents C 1-10 alkyl, said alkyl optionally substituted with 1 to 3 groups of OH and C 6-10 aryl.

76. The compound of claim 73 , wherein:

A and X each represents hydrogen;

R 1 represents C 1-10 alkyl, said alkyl optionally substituted with 1 to 3 groups of OH and CF 3 .

77. The compound of claim 73 , wherein:

A and X each represents hydrogen;

R 1 represents hydrogen or CH(OH)CH 3 .

78. A compound of structural forumla I:

or a pharmaceutically acceptable salt, enantiomer or diatereomer thereof, wherein:

A and X each represents hydrogen;

each R a independently represents C 1-6 alkyl, halogen, hydroxyl, (CH 2 ) n CF 3 , OCHF 2 , OCF 3 , c 3-6 cycloalkyl, O(CH 2 ) n C 3-6 cycloalkyl, NR 2 C(O)R 2 , C(O)N(R 2 ) 2 , C(R 2 ) 2 OR 2 , C(O)R 2 , NO 2 , CN, N(R 2 ) 2 , (CH 2 ) n C(O)OR 2 , SO 2 R 2 , OR 2 , (CH 2 ) n C 5-10 heterocyclyl, NH(CH 2 ) n C 5-10 heterocyclyl, (CH 2 ) n C 6-10 aryl, O(CH 2 ) n C 6-10 aryl, or O(CH 2 ) n C 5-10 heterocyclyl, said cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of R b ;

each R b independently represents C 1-6 alkyl, halogen, CHF 2 , N(R 2 ) 2 , CH 2 OH, OR 2 , (CH 2 ) n CF 3 , or CN;

R 1 represents NR 2 R 3 ;

each of R 2 and R 3 independently represent H or C 1-6 alkyl; and

n represents 0 to 5.

79. The compound according to claim 1 which is:

1-biphenyl-3-yl-2-(2-biphenyl-2-yl-2-hydroxyethyl)-5-hydroxypyridin-4(1H)-one;

2-[cyclohexyl(hydroxy)methyl]-5-hydroxy-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-2-(cyclopentylmethyl)-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-(2-cyclopropylethyl)-5-hydroxypyridin-4(1H)-one;

2-[cyclopropyl(hydroxy)methyl]-5-hydroxy-1-(3-isoquinolin-4-ylphenyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-2-[2-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-1-methylethyl]-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-(difluoromethyl)-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-2-(dimethylamino)-5-hydroxypyridin-4(1H)-one;

5-hydroxy-2-(2-hydroxy-1,3-dimethylbutyl)-1-phenylpyridin-4(1H)-one;

1-biphenyl-3-yl-2-(fluoromethyl)-5-hydroxypyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-(methoxymethyl)pyridin-4(1H)-one;

1-biphenyl-3-yl-5-hydroxy-2-methylethyl)pyridin-4(1H)-one;

1-(2′-fluorobiphenyl-3-yl)-5-hydroxy-2-methylethyl)pyridin-4(1H)-one;

5-hydroxy-2-(1-methylethyl)-1-(3-pyridin-3-ylphenyl)pyridin-4(1H)-one;

1-[3-(6-fluoropyridin-3-yl)phenyl]-5-hydroxy-2-methylethyl)pyridin-4(1H)-one;