Pyrazolyl pyrimidinone compounds as PDE2 inhibitors

1. A compound represented by structural formula I:

A-Y—R 2 —R 3    I

or a pharmaceutically acceptable salt or solvate thereof, wherein:

A is a pyrimidinone optionally substituted with 1 to 2 groups of R 1 ;

Y is pyrazolyl optionally substituted with 1 to 2 groups of R b ;

R 1 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-10 cycloalkyl, and (CH 2 ) n C 6-10 aryl, said alkyl and aryl optionally substituted with one to three groups of R a ;

R 2 is selected from the group consisting of —C(═O)—, and CR x R Y ;

R X and R Y are independently selected from the group consisting of H, (CH 2 ) n OR, C 1 - 6 alkyl, C(O)OR and N(R) 2 , said alkyl optionally substituted with one to three groups of R a ;

or R X and R Y can combine with the carbon atom to which they are attached to form a group selected from —O—, C 2-6 alkenyl, C 3-6 cycloalkyl and C 3-6 heterocyclyl;

R represents H, or C 1-6 alkyl,

R 3 is C 4-10 heterocyclyl or C 6-10 aryl, said heterocyclyl and aryl optionally substituted with one to three groups of R a ;

or R 2 and R 3 can combine to form a C 3-10 heterocyclyl, said heterocyclyl optionally substituted with one to three groups of R a ;

R a is selected from the group consisting of H, halo, CN, C 1-6 alkyl, (CH 2 ) n OR, (O)p C 1-4 haloalkyl, C(O)OR, —O(CH 2 ) n N(R) 2 , (CHR) n N(R) 2 , NO 2 , SCF 3 , S(O) s CF 3 , S(O) s R, SF 5 , C 3-10 cycloalkyl, C 5-10 heterocyclyl, and C 6-10 aryl, said alkyl, cycloalkyl, heterocyclyl and aryl optionally substituted with one to three groups of R b ;

R b is selected from the group consisting of H, halo, C 1-6 alkyl, (CH 2 ) n OR, and (O) p C 1-4 haloalkyl;

n represents 0, 1, 2, 3, or 4;

s represents 0, 1, or 2; and

p represents 0 or 1.

2. The compound according to claim 1 wherein A is represented by A1:

wherein R 1 is as originally described and R z is hydrogen or, C 1-6 alkyl.

3. The compound according to claim 1 wherein R 2 is CR x R Y .

4. The compound according to claim 1 wherein R 2 is selected from the group consisting of optionally substituted methyl, ethyl isopropyl, propyl, butyl, isobutyl, pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and (CH 2 ) n phenyl.

5. The compound according to claim 2 wherein R 1 is methyl and Rz is hydrogen.

6. The compound according to claim 3 wherein R x and R Y are independently selected from the group consisting of H, (CH 2 ) n OR, C 1-6 alkyl, C(O)OR and N(R) 2 , said alkyl optionally substituted with one to three groups of R a. .

7. The compound according to claim 6 wherein one of R x and R Y is hydrogen and the other is selected from selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, (CH 2 ) n OH, C(O)OR, NHCH 3 , NH 2 , NHCH 2 CH 3 , OCH 3 , O(CH 2 ) n CH 3 , said methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and pentyl said methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and pentyl optionally substituted with 1 to 3 groups of OH.

8. The compound according to claim 1 wherein R x and R Y together with the carbon atom to which they are attached combined to form a group selected from —C(═O)—, C 2-6 alkenyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuranyl.

9. The compound according to claim 1 wherein R 3 is optionally substituted C 4-10 heterocyclyl.

10. The compound according to claim 9 wherein R 3 is selected from the group consisting of optionally substituted dihydroisochromenyl, dihydrobenzofuranyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl, and piperidinyl.

11. The compound according to claim 1 wherein R 3 is optionally substituted C 6-10 aryl.

12. The compound according to claim 11 wherein R 3 is optionally substituted phenyl.

13. The compound according to claim 1 wherein R 2 and R 3 combine to form a C 3-10 heterocyclyl selected from the group consisting of tetrahydrofuranyl and tetrahydrobenzfuranyl.

14. The compound according to claim 1 represented by structural formula Ia:

or a pharmaceutically acceptable salt or hydrate thereof wherein R 1 is selected from the group consisting of optionally substituted hydrogen, C 1-6 alkyl, cyclopropyl, cyclobutyl, and phenyl and R 2 is CR X R Y wherein one of R X and R Y .is hydrogen and the other is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, (CH 2 ) n OH, C(O)OR, NHCH 3 , NH 2 , NHCH 2 CH 3 , OCH 3 , O(CH2) n Ch 3 , said methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and pentyl optionally substituted with 1 to 3 groups of OH.

15. The compound according to claim 14 wherein R 3 is optionally substituted methyl, ethyl, propyl, isopropyl, butyl, isobutyl, dihydroisochromenyl, dihydrobenzofuranyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, naphthyl, and phenyl.

16. The compound according to claim 15 wherein R 3 is optionally substituted phenyl.

17. The compound according to claim 14 wherein R 2 and R 3 combine to form a C 3-10 heterocyclyl selected from the group consisting of tetrahydrofuranyl and tetrahydrobenzfuranyl.

18. A compound which is:

6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]propyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]-2-methylpropyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

2-benzyl-6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-(1-methylethyl)pyrimidin-4(3H)-one,

6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-(1-methylethyl)pyrimidin-4(3H)-one,

2-ethyl-6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]cyclobutyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-{4-[1-(4-cyclobutylphenyl)ethyl]-1H-pyrazol- 1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[1-(4-cyclopropylphenyl)ethyl]-1H-pyrazol- 1-yl}-2-methylpyrimidin-4(3H)-one,

2-methyl-6-(4-{1-[4-(1-methylcyclopropyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

6-(4-{1-[4-(2-methoxyethyl)phenyl]ethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-{4-[1-(3,4-dihydro-1H-isochromen-6-yl)ethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

2-methyl-6-{4-[1-(4-propylphenyl)ethyl]-1H-pyrazol-1-yl }pyrimidin-4(3H)-one,

6-(4-{1-[4-(1-ethylcyclopropyl)phenyl]ethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-{4-[1-(4-tert-butylphenyl)ethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[1-(3,4-dihydro-1H-isochromen-7-yl)ethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[1-(3,3-dimethyl-2,3 -dihydro-1-benzofuran-6-yl)ethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

2-methyl-6-{4-[4-(trifluoromethoxy)benzyl]-1H-pyrazol-1-yl}pyrimidin-4(3H)-one,

2-methyl-6-{1-methyl-5-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-4-yl}pyrimidin-4(3H)-one,

2-methyl-6-{1-[4-(trifluoromethoxy)benzyl]-1H-pyrazol-4-yl}pyrimidin-4(3H)-one,

2-methyl-6-(4-{[4-(trifluoromethyl)phenyl]carbonyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-{4-[4-(trifluoromethyl)benzyl]-1H-pyrazol- 1-yl}pyrimidin-4(3H)-one,

2-phenyl-6-{1-[4-(trifluoromethoxy)benzyl]-1H-pyrazol-4-yl}pyrimidin-4(3H)-one,

2-phenyl-6-{4-[4-(trifluoromethyl)benzyl]-1H-pyrazol-1-yl}pyrimidin-4(3H)-one,

2-phenyl-6-(4-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol- 1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol- 1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(3 -{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(3-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

2-methyl-6-(3-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

2-methyl-6-(3-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

6-(4-ethyl-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{1-[3-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-(3-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(3-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

6-(4-{(1R)-1-[3-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1S)-1-[3-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6(4-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-[4-(1-pyridin-4-ylethyl)-1H-pyrazol-1-yl]pyrimidin-4(3H)-one,

2-methyl-6-(4-{2-[4-(trifluoromethyl)phenyl]tetrahydrofuran-2-yl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{(2R)-2-[4-(trifluoromethyl)phenyl]tetrahydrofuran-2-yl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{(2S)-2-[4-(trifluoromethyl)phenyl]tetrahydrofuran-2-yl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{1-[2-methyl-4-(trifluoromethyl)phenyl]ethenyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-{4-[1-methyl-5-(trifluoromethyl)-1,3-dihydro-2-benzofuran-1-yl]-1H-pyrazol-1-yl}pyrimidin-4(3H)-one,

2-methyl-6-(4-{1-[2-methyl-4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

6-(4-{4-hydroxy-4-methyl-2-]4-(trifluoromethyl)phenyl]tetrahydrofuran-2-yl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-{4-[(1S)-1-methyl-5-(trifluoromethyl)-1,3-dihydro-2-benzofuran-1-yl]-1H-pyrazol-1-yl}pyrimidin-4(3H)-one,

2-methyl-6-{4-[(1R)-1-methyl-5-(trifluoromethyl)-1,3-dihydro-2-benzofuran-1-yl]-1H-pyrazol-1-yl}pyrimidin-4(3H)-one,

6-(4-{1-[2-fluoro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{1-[2-fluoro-4-(trifluoromethyl)phenyl]-1-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-1-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-1-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-(1-{(1R)-1-[2-methyl-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{(1S)-1-[2-methyl-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-methoxy-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-methoxy-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-fluoro-4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(1-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(1-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{(1R)-1-[4-(pentafluoro-lambda˜6˜-sulfanyl)phenyl]ethyl}1-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{(1S)-1-[4-(pentafluoro-lambda˜6˜-sulfanyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(1-{(1R)-1-[4-(pentafluoro-lambda˜6˜-sulfanyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(1-{(1S)-1-(pentafluoro-lambda˜6˜-sulfanyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(1-{(1S)-1-[2fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one,

2-methyl-6-{1-[1-(tetrahydro-2H-pyran-4-yl)ethyl]-1H-pyrazol-4-yl}pyrimidin-4(3H)-one,

2-methyl-6-(4-{[4-(trifluoromethyl)piperidin-1-yl]methyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-cyclopropyl-6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-cyclopropyl-6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2,3-dimethyl-6-(4-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[3-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-3 -yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

6-(3,5-dimethyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-(3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(5-methyl-1-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(5-methyl-1-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-cyclopropyl-6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-chloro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-chloro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

2-ethyl-6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-ethyl-6-(1-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-(1-{(1R)-1-[4-(difluoromethoxy)-2-fluorophenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[4-(difluoromethoxy)-2-fluorophenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[4-(difluoromethoxy)-2-methylphenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[4-(difluoromethoxy)-2-methylphenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(4-cyclopropyl-2-fluorophenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(4-cyclopropyl-2-fluorophenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(4-cyclopropyl-2-methylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(4-cyclopropyl-2-methylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-fluoro-4-(2,2,2-trifluoroethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-fluoro-4-(2,2,2-trifluoroethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-fluoro-4-(methoxymethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-fluoro-4-(methoxymethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(2-chloro-4-ethylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(2-chloro-4-ethylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(4-ethyl-2-fluorophenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(4-ethyl-2-fluorophenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-chloro-4-(methoxymethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-chloro-4-(methoxymethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-(1-{(1R)-1-[2-methyl-4-(2,2,2-trifluoroethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one

2-methyl-6-(1-{(1S)-1-[2-methyl-4-(2,2,2-trifluoroethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-{1-[(1R)-1-(2-chloro-4-cyclopropylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(2-chloro-4-cyclopropylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2,6-difluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-{4-[(1R)-1-(2-fluoro-4-propylphenyl)-1-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[(1S)-1-(2-fluoro-4-propylphenyl)-1-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(4-ethyl-2-fluorophenyl)-2-hydroxyethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(4-ethyl-2-fluorophenyl)-2-hydroxyethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

methyl [2-fluoro-4-(trifluoromethyl)phenyl][4-(2-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-1H-pyrazol-1-yl]acetate,

methyl (2-chloro-4-ethylphenyl)[4-(2-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-1H-pyrazol-1-yl]acetate,

6-{4-[(1S)-1-(4-ethyl-2-fluorophenyl)-2-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[(1R)-1-(4-ethyl-2-fluorophenyl)-2-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(2-chloro-4-ethylphenyl)-2-hydroxyethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(2-chloro-4-ethylphenyl)-2-hydroxyethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-(4-{(1R)-1-[2-chloro-4-(trifluoromethyl)phenyl]-1-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1S)-1-[2-chloro-4-(trifluoromethyl)phenyl]-1-hydroxyethyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-{4-[(1R)-1-(4-ethyl-2-fluorophenyl)-1-hydroxyethyl]-1H-pyrazol-1-yl 1-2-methylpyrimidin-4(3H)-one,

6-{4-[(1S)-1-(4-ethyl-2-fluorophenyl)-1-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[1-(2-chloro-4-ethylphenyl)-1-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[(1S)-1-(2-chloro-4-ethylphenyl)-2-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-{4-[(1R)-1-(2-chloro-4-ethylphenyl)-2-hydroxyethyl]-1H-pyrazol-1-yl}-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-chloro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-chloro-4-(trifluoromethyl)phenyl]-2-hydroxyethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-hydroxypropyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

6-(4-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-hydroxypropyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{(1S)-1-[4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{(1R)-1-[4-(trifluoromethoxy)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{1-[4-(trifluoromethyl)phenyl]propyl}-1- 1H-pyrazol- 1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{2-methyl-1-[4-(trifluoromethyl)phenyl]propyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-methyl-3-{1-[4-(trifluoromethyl)phenyl]ethyl}-1-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{(methylamino)[4-(trifluoromethyl)phenyl]methyl}-1-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-methyl-6-(4-{(methylamino)[4-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

6-(4-{methoxy [4-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-1-yl)-2-methylpyrimidin-4(3H)-one,

2-methyl-6-(1-methyl-3-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-methyl-3-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-5-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-methyl-5-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-methyl-5-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-methyl-5-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(3-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(3-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(3-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

6-(1-{1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(4-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

2-(3,4-dimethoxybenzyl)-6-(4-{1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-1-yl)pyrimidin-4(3H)-one,

6-(1{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-(4-methoxybenzyl)pyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-(4-methoxybenzyl)pyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-(3-methoxybenzyl)pyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-(3-methoxybenzyl)pyrimidin-4(3H)-one,

2-(4-fluoro-3-methoxybenzyl)-6-(1-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(4-fluoro-3-methoxybenzyl)-6-(1-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-(1-{(1S)-1-[2,4-bis(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

6-(1-{(1R)-1-[2,4-bis(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

2-(3-fluoro-4-methoxybenzyl)-6-(1-{(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

2-(3-fluoro-4-methoxybenzyl)-6-(1-{(1R)-1-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

6-{1-[(1S)-1-(2-chloro-4-methylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(2-chloro-4-methylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1S)-1-(2-fluoro-4-methylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[(1R)-1-(2-fluoro-4-methylphenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

6-{1-[1-(4-fluorophenyl)ethyl]-1H-pyrazol-4-yl}-2-methylpyrimidin-4(3H)-one,

2-methyl-6-{1-(4-methylphenyl)ethyl]-1H-pyrazol-4-pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-(trifluoromethyl)phenyl]butyl}-1H-pyrazol-4-yl)pyrimidin-4(3H)-one,

methyl 4-{1-[4-(2-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}benzoate,

2-methyl-6-[1-(1-phenylethyl)-1H-pyrazol-4-yl]pyrimidin-4(3H)-one,

2-methyl-6-{1-[1-(4-methylphenyl)ethyl]-1H-pyrazol-3-yl}pyrimidin-4(3H)-one,

2-methyl-6-[1-(1-phenylethyl)-1H-pyrazol-3-yl]pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[3-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

2-methyl-6-(1-{1-[4-(trifluoromethyl)phenyl]butyl}-1H-pyrazol-3-yl)pyrimidin-4(3H)-one,

6-{1-[1-(4-fluorophenyl)ethyl]-1H-pyrazol-3-yl}-2-methylpyrimidin-4(3H)-one,

methyl 4-{1-[3-(2-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}benzoate,

6-(1-{(1R)-1-[2,6-difluoro-4-(trifluoromethyl)phenyl]ethyl}-1H-pyrazol-4-yl)-2-methylpyrimidin-4(3H)-one,

or a pharmaceutically acceptable salt and hydrate thereof.

19. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.