Pyrimidinone amide compounds as PDE2 inhibitors

1. A compound represented by structural formula I:

or a pharmaceutically

acceptable salt thereof,

wherein:

R 1 is linked to the pyrimidinone via an atom other than carbon and is selected from the group consisting of halo, —OR, O(CH 2 ) 1-3 OR, O(CH 2 ) 1-3 N(R) 2 , O(CH 2 ) n C(R) 2 OR, O-(CH 2 ) n C 4-10 heterocyclyl, O-(CH 2 ) 1-3 OC 6-10 aryl, O—C 6-10 aryl, N(R x ) 2 , —NRC 5-10 heterocyclyl, —NRC 6-10 aryl, —NRC 3-10 cycloalkyl, SR, said alkyl, cycloalkyl, heterocyclyl and aryl optionally substituted with one to three groups of R a ;

R 1a represents H, or C 1-6 alkyl, said alkyl optionally substituted with OH or halo,

R 2 and R 3 are independently selected from the group consisting of hydrogen, C 1-6 alkyl, (CH 2 ) n CN, C(O)R, C(O)OR, CF 3 , —C 3-10 cycloalkyl, C 6-10 aryl, C 5-10 heteroaryl, said alkyl, cycloalkyl, aryl and heteroaryl optionally substituted with one to three groups of R b ;

R 2 and R 3 can combine with the carbon atom to which they are attached to form a C 3-6 cycloalkyl, said cycloalkyl optionally interrupted with 1-2 heteroatoms selected from O, S, or N and optionally substituted with one to three groups of R b

R 4 represents hydrogen, halo, or C 1-6 alkyl; or alternatively,

R 2 and R 3 along with the carbon atom to which they are attached and the R 4 on the phenyl ring can combine to form a C6-10 bicyclic ring which includes the phenyl ring, said bicyclic ring optionally interrupted with 1-2 heteroatoms selected from O, S, and N and optionally substituted with one to three groups of R b ;

R represents H, or C 1-6 alkyl;

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, S(O) s CF 3 , S(O) s R, SF 5 , C 3-10 cycloalkyl, said alkyl and cycloalkyl 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, SO 2 C 1-6 alkyl, and (O) p C 1-4 haloalkyl;

each occurring R x independently represents H, or C 1-6 alkyl, or two adjacent R x groups can combined together with the nitrogen atom to which they are attached to form a C 4-10 heterocyclyl optionally substituted with one to three groups of R b ;

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 or a pharmaceutically acceptable salt thereof wherein R 1a is hydrogen.

3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of OR, O(CH 2 ) 1-3 OR, O(CH 2 ) n C(R) 2 OR, and O(CH 2 ) 1-3 N(R) 2 and optionally substituted O—(CH 2 ) n C 4-10 heterocyclyl said heterocyclyl is selected from the group consisting of oxetanyl, tetrahydrofuranyl, piperidinyl, pyrrolidinyl, morpholinyl, dihydropyrrolopyrazolyl, dihydropyrrolopyrimindyl, tetrahydropyranyl, pyrazolyl, and azetidinyl.

4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group N(R x ) 2 , —NRC 5-10 heterocyclyl, —NRC 6-10 aryl, and NRC 3-10 cycloalkyl, said cycloalkyl, aryl and heterocyclyl optionally substituted with one to three groups of R a .

5. The compound according to claim 4 or a pharmaceutically acceptable salt thereof wherein R 1 is N(R x ) 2 and the two adjacent R x groups are combined together with the nitrogen atom to which they are attached to form a C 4-10 heterocyclyl selected from the group consisting of optionally substituted pyrrolidinyl, pyrazolyl, azetidinyl, piperidinyl, morpholinyl, dihydropyrrolopyrazolyl, dihydropyrrolopyrimidinyl, and dihydropyrrolopyridinyl.

6. The compound according to claim 3 or a pharmaceutically acceptable salt thereof wherein R 1 is O-(CH 2 ) n C 4-10 heterocyclyl, said heterocyclyl optionally substituted with one to three groups of R a .

7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from the group consisting of SCH 3 , —N(CH 3 ) 2 , N(CH 3 )(CH 2 CH 3 ), N(CH 2 CH 3 ) 2 , —NH 2 , —NHCH 3 , NH-cyclobutyl, NH-cyclopentyl, NH-cyclopropyl, NH-pyridyl, —OR, —O-phenyl, —O(CH 2 ) 2 OCH 3 , —O(CH 2 ) 3 OCH 3 , —O(CH 2 ) 3 OCH(CH 3 ) 2 , —O(CH 2 ) 2 N(CH 3 ) 2 , —O(CH 2 ) 2 C(CH 3 ) 2 OCH 3 , —OCH 2 oxetanyl, —O(CH 2 ) 4 OCH 3 , —O(CH 2 ) 3 NHCH 3 , —O-tetrahydrofuranyl, —O-piperidinyl, —O-oxetanyl, —O(CH 2 ) 3 Ophenyl, O(CH 2 ) 2 CH(CH 3 )OCH 3 , —O-tetrahydropyranyl, O-pyrrolidinyl, N linked pyrazolyl, N linked azetidinyl, N linked pyrrolidinyl, and N linked piperidinyl, said cyclobutyl, cyclopentyl, cyclopropyl, phenyl, oxetanyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, pyrollidinyl, pyrazolyl, and azetidinyl optionally substituted with one to three groups of R a .

8. The compound according to claim 7 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from N(CH 3 ) 2 , N(CH 3 )(CH 2 CH 3 ), N(CH 2 CH 3 ) 2 , —NH 2 , —NHCH 3 , and optionally substitiuted NH-cyclobutyl, NH-cyclopentyl, NH-cyclopropyl, and NH-pyridyl.

9. The compound according to claim 8 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from N(CH 3 ) 2 .

10. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein one of R 2 and R 3 is hydrogen or CH 3 and the other is C 1-6 alkyl or C 3-10 cycloalkyl, said alkyl and cycloalkyl optionally substituted with one to three groups of R b .

11. The compound according to claim 10 or a pharmaceutically acceptable salt thereof wherein the C 1-6 alkyl is selected from the group consisting of CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 , C(CH 3 ) 3 and the optionally substituted C 3-10 cycloalkyl is selected from cyclopropyl, cyclobutyl, and cyclopentyl.

12. The compound according to claim 11 or a pharmaceutically acceptable salt thereof wherein the C 1-6 alkyl is selected from the group consisting of CH 3 , CH(CH 3 ) 2 , and CH 2 CH 3 , and the optionally substituted C 3-10 cycloalkyl is cyclopropyl.

13. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R 2 and R 3 combine with the carbon atom to which they are attached to form a C 3-10 cycloalkyl, said cycloalkyl optionally substituted with one to three groups of R b .

14. The compound according to claim 13 wherein the C 3-10 cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, and cyclopentyl.

15. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R a is selected from OH, halo, CH 3 , optionally substituted cyclopropyl, (CH 2 ) n OCH 3 , CH 2 F, (CH 2 ) n CF 3 , OCHF 2 , OCF 3 , SCH 3 , SCF 3 , SF 5 , SOCF 3 , SO 2 CF 3 , SO 2 CH 3 , CH 2 NH 2 , and (CH 2 ) n N(CH 3 ) 2 .

16. The compound according claim 1 or a pharmaceutically acceptable salt thereof represented by structural formula II:

wherein R 1 is selected from the group consisting of —N(CH 3 ) 2 , NH 2 , NHCH 3 , O(CH 2 ) 3 NHCH 3 , and optionally substituted O-tetrahydrofuranyl, N linked pyrazolyl, N linked pyrrolidinyl, O-pyrrolidinyl, or O-piperidinyl, R 3 is selected from the group consisting of CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 , C(CH 3 ) 3 and optionally substituted cyclopropyl, and R a is selected from the group consisting of SCF 3 , CF 3 , OCF 2 , OCF 3 , and CH 2 CF 3 .

17. A compound which is:

N-(1-(3-fluoro-4-(trifluoromethyl)phenyl)cyclopropyl)-6-oxo-2-(pyrrolidin-1-yl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-N-(2,2-dimethyl-1-(4-(trifluoromethyl)phenyl)propyl)-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-N-(1-(3-chloro-4-(trifluoromethoxy)phenyl)ethyl)-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-N-(cyclopropyl(4-(pentafluoro-λ 6 -sulfanyl)phenyl)methyl)-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-6-oxo-N-(1-(4-(pentafluoro-λ 6 -sulfanyl)phenyl)propyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-6-oxo-2-(pyrrolidin-1-yl)-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(4-methyl-1H-pyrazol-1-yl)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(3-methyl-1H-pyrazol-1-yl)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-6-oxo-2-(1H-pyrazol-1-yl)-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(azetidin-1-yl)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

2-((R)-3-fluoropyrrolidin-1-yl)-6-oxo-N-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

2-((S)-3-fluoropyrrolidin-1-yl)-6-oxo-N-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(3,3-difluoropyrrolidin-1-yl)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

N-((R)-2,2-dimethyl-1-(4-(trifluoromethyl)phenyl)propyl)-2-(3-(methoxymethyl)pyrrolidin-1-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(methylthio)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(methylthio)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-methoxy-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-ethoxy-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-6-oxo-2-phenoxy-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-hydroxy-N-(2-methyl-1-(4-((trifluoromethyl)thio)phenyl)propyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(2-Methoxyethoxy)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4- carboxamide,

(R)-2-(3,4-dimethoxyphenoxy)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide,

2-(3-Fluoroazetidin-1-yl)-6-oxo-N-{(1R)-1[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(3,3-Difluoroazetidin-1-yl)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[3-fluoro-4-(trifluoromethoxy)phenyl]methyl}-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(trifluoromethyl)phenyl]methyl}-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-cyclopropyl{4-[(trifluoromethyl)sulfanyl]phenyl}methyl]-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

6-oxo-2-pyrrolidin-1-yl-N-{(1R)-1-[4-(trifluoromethoxy)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

N-[(1R)-1-{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-[(1R)-2-methyl-1-{4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-2,2-dimethyl-1-[4-(2,2,2-trifluoroethyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(difluoromethoxy)phenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethoxy)phenyl]-2-methylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethoxy)phenyl]-2,2-dimethylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(1R)-1-(4-cyclopropylphenyl)-2,2-dimethylpropyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[2,5-difluoro-4-(trifluoromethyl)phenyl]ethyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-2,2-dimethylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-2,2-dimethyl-1-[4-(pentafluoro-λ 6 -sulfanyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1,2-dimethyl-1-[4-(pentafluoro-λ 6 -sulfanyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(1R)-1-(4-cyclopropyl-3-fluorophenyl)ethyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-[(R)-[3-fluoro-4-(trifluoromethyl)phenyl](1-methylcyclopropyl)methyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(R)-(1-methylcyclopropyl)[4-(trifluoromethyl)phenyl]methyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-(4-tert-butylphenyl)(1-methylcyclopropyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{1-[4-(pentafluoro-λ 6 -sulfanyl)phenyl]cyclopropyl}-1,6-dihydropyrimidine-4-carboxamide,

N-[1-(4-tert-butylphenyl)cyclopropyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-2-methyl-1-[4-(trifluoromethyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethoxy)-3-fluorophenyl]-2-methylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1-[2-fluoro-4-(trifluoromethyl)phenyl]cyclopropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[1-(4-tert-butoxyphenyl)cyclopropyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{1-[4-(2,2,2-trifluoroethyl)phenyl]cyclopropyl}-1,6-dihydropyrimidine-4-carboxamide,

N-{1-[4-(difluoromethoxy)phenyl]cyclopropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(difluoromethoxy)-3-fluorophenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethoxy)-3-fluorophenyl]-2,2-dimethylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-[4-(difluoromethoxy)-3-fluorophenyl](1-methylcyclopropyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-cyclopropyl(4-cyclopropyl-3-fluorophenyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(R)-(1-methylcyclopropyl)[4-(pentafluoro-λ 6 -sulfanyl)phenyl]methyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(1R)-1-(4-cyclopropyl-3-fluorophenyl)-2,2-dimethylpropyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-[4-(difluoromethyl)-3-fluorophenyl](1-methylcyclopropyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethyl)phenyl]-2,2-dimethylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-[4-(difluoromethyl)phenyl](1-methylcyclopropyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethyl)-3-fluorophenyl]-2,2-dimethylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethyl)phenyl]-2-methylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(difluoromethyl)phenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethyl)-3-fluorophenyl]-2-methylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(difluoromethyl)-3-fluorophenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethyl)phenyl]propyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethyl)-3-fluorophenyl]propyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{1-[4-(difluoromethyl)-3-fluorophenyl]-1-methylethyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{1-[4-(difluoromethyl)-3-fluorophenyl]cyclopropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-(4-cyclopropylphenyl)(1-methylcyclopropyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1S)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(difluoromethyl)-2-fluorophenyl]-2,2-dimethylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(1,1-difluoroethyl)phenyl]ethyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(1,1-difluoroethyl)phenyl]-2-methylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(1,1-difluoroethyl)phenyl]-2,2-dimethylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[4-(1,1-difluoroethyl)-3-fluorophenyl]-2-methylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1-methyl-1-[2-methyl-4-(trifluoromethyl)phenyl]ethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1-[2-methoxy-4-(trifluoromethyl)phenyl]-1-methylethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{1-[2-chloro-4-(trifluoromethyl)phenyl]-1-methylethyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1-[2-fluoro-4-(trifluoromethoxy)phenyl]-1-methylethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1-[2-fluoro-4-(trifluoromethyl)phenyl]-1-methylethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[2-fluoro-4-(trifluoromethoxy)phenyl]ethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[2,3-difluoro-4-(trifluoromethyl)phenyl]ethyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-[3-chloro-4-(trifluoromethoxy)phenyl](cyclopropyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[3-chloro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethoxy)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-[(1R)-1-{4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{(1R)-1-[4-(pentafluoro-λ 6 -sulfanyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]ethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-2-methyl-1-[4-(trifluoromethoxy)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-(1-{4-[(trifluoromethyl)sulfanyl]phenyl}cyclopropyl)-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1-[3-fluoro-4-(trifluoromethyl)phenyl]-1-methylethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{1-[3-fluoro-4-(trifluoromethyl)phenyl]cyclopropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-2-methyl-1-[4-(trifluoromethyl)phenyl]propyl}-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-[(1R)-1-{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}ethyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-cyclopropyl{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-[(1R)-1-{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(pentafluoro-λ 6 -sulfanyl)phenyl]methyl}-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethoxy)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2,2-dimethylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[3-fluoro-4-(trifluoromethyl)phenyl]-2,2-dimethylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-[(1R)-2,2-dimethyl-1-{4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethoxy)phenyl]propyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[3-fluoro-4-(trifluoromethyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(trifluoromethoxy)phenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(trifluoromethyl)phenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[3-fluoro-4-(trifluoromethyl)phenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[3-fluoro-4-(trifluoromethoxy)phenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-cyclopropyl{4-[(trifluoromethyl)sulfanyl]phenyl}methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[3-fluoro-4-(trifluoromethyl)phenyl]-2-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-cyclopropyl(4-cyclopropylphenyl)methyl]-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(trifluoromethoxy)phenyl]methyl}-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

N-[(R)-cyclopropyl (4-cyclopropylphenyl)methyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-N-(1-(4-(pentafluorothio)-2-fluorophenyl)ethyl)-6-oxo-1,6-dihydrop-yrimidine-4-carboxamide,

(S)-2-(dimethylamino)-N-(1-(4-(pentafluorothio)-2-fluorophenyl)ethyl)-6-oxo-1,6-dihydropy-rimidine-4-carboxamide,

2-(Dimethylamino)-N-{1-methyl-1-[4-(pentafluoro-λ 6 -sulfanyl)phenyl]ethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(dimethylamino)-N-[{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}(1-methylcyclopropyl)methyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-N-[{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}(1-methylcyclopropyl)methyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(dimethylamino)-6-oxo-N-{1-[4-(2,2,2-trifluoro-1,1-dimethylethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-6-oxo-N-{1-[4-(2,2,2-trifluoro-1,1-dimethylethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(dimethylamino)-N-{1-[3-fluoro-4-(1-methylcyclopropyl)phenyl]-2,2-dimethylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-N-{1-[3-fluoro-4-(1-methylcyclopropyl)phenyl]-2,2-dimethylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(dimethylamino)-6-oxo-N-[1-{4-[1-(trifluoromethyl)cyclopropyl]phenyl}ethyl]-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-6-oxo-N-[1-{4-[1-(trifluoromethyl)cyclopropyl]phenyl}ethyl]-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(dimethylamino)-N-{1-[2-fluoro-4-(pentafluoro-λ 6 -sulfanyl)phenyl]-2,2-dimethylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-N-{1-[2-fluoro-4-(pentafluoro-λ 6 -sulfanyl)phenyl]-2,2-dimethylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(dimethylamino)-N-{1-[2-fluoro-4-(trifluoromethyl)phenyl]-1-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-N-{1-[2-fluoro-4-(trifluoromethyl)phenyl]-1-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

6-oxo-2-piperidin-1-yl-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-morpholin-4-yl-6-oxo-N-{(1 R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-amino-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(methylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

6-oxo-2-(pyridin-2-ylamino)-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]-6-oxo-N-{(1R)-1- [4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(cyclobutylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(cyclopentylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(cyclopropylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-[ethyl(methyl)amino]-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(diethylamino)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-[(1R)-1-{4-[(trifluoromethyl)sulfanyl]phenyl}ethyl]-1,6-dihydropyrimidine-4-carboxamide,

2-(methylamino)-6-oxo-N-[(1R)-1-{4-[(trifluoromethyl)sulfanyl]phenyl}ethyl]-1,6-dihydropyrimidine-4-carboxamide,

2-amino-6-oxo-N-[(1R)-1-{4-[(trifluoromethyl)sulfanyl]phenyl}ethyl]-1,6-dihydropyrimidine-4-carboxamide,

6-oxo-2-pyrrolidin-1-yl-N-[(1R)-1-{4-[(trifluoromethyl)sulfanyl]phenyl}ethyl]-1,6-dihydropyrimidine-4-carboxamide,

N-[(1R)-2-methyl-1-{4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-2-pyrrolidin-1-yl-1,6-dihydropyrimidine-4-carboxamide,

2-azetidin-1-yl-N-[(1R)-2-methyl-1-{4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-[(1R)-1-{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}-2-methylpropyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-2-(methylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-amino-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(methylamino)-N-[(1R)-2-methyl-1-{4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-amino-N-[(1R)-2-methyl-1-{4-[(trifluoromethyl)sulfanyl]phenyl}propyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-[(1R)-1-{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}-2-methylpropyl]-2-(methylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-amino-N-[(1R)-1-{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}-2-methylpropyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-amino-N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-2-(methylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(2-methyl-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-[(3S)-3-fluoropyrrolidin-1-yl]-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-[(3R)-3-fluoropyrrolidin-1-yl]-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(3-fluoroazetidin-1-yl)-N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-[(3S)-3-fluoropyrrolidin-1-yl]-N-[(1R)-1-{3-fluoro-4-[(trifluoromethyl)sulfanyl]phenyl}-2-methylpropyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpropyl}-2-[(3R)-3-hydroxypyrrolidin-1-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(R)-cyclopropyl[4-(trifluoromethyl)phenyl]methyl}-2-[(3S)-3-fluoropyrrolidin-1-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-[(3S)-3-fluoropyrrolidin-1-yl]-N-{(1R)-1-[3-fluoro-4-(trifluoromethyl)phenyl]-2-methylpropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-2-[(3S)-3-fluoropyrrolidin-1-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-2-[(3S)-3-methoxypyrrolidin-1-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-2-[(3R)-3-methoxypyrrolidin-1-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(R)-2-(dimethylamino)-N-{1,2-dimethyl-1-[4-(pentafluoro-λ 6 -sulfanyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(S)-2-(dimethylamino)-N-{1,2-dimethyl-1-[4-(pentafluoro-λ 6 -sulfanyl)phenyl]propyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-N-{2-methyl-1-[4-(trifluoromethyl)phenyl]cyclopropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide (cis, enantiomer A),

2-(dimethylamino)-N-{2-methyl-1-[4-(trifluoromethyl)phenyl]cyclopropyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide (cis, enantiomer B),

(R)-N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-2-[3-(methoxymethyl)pyrrolidin-1-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

(S)-N-{(1R)-2,2-dimethyl-1-[4-(trifluoromethyl)phenyl]propyl}-2-[3-(methoxymethyl)pyrrolidin-1-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

6-oxo-2-propoxy-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(3-methoxypropoxy)-6-oxo-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-[(1-methylpiperidin-3-yl)oxy]-6-oxo-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-[3-(1-methylethoxy)propoxy]-6-oxo-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(3-methoxy-3-methylbutoxy)-6-oxo-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-[2-(methylamino)ethoxy]-6-oxo-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

6-oxo-2-(tetrahydrofuran-3-yloxy)-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-[3-(4-methoxyphenoxy)propoxy]-6-oxo-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

N-[(1R)-1-(4-cyclopropyl-3-fluorophenyl)-2-methylpropyl]-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{phenyl[4-(trifluoromethyl)phenyl]methyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{pyridin-4-yl[4-(trifluoromethyl)phenyl]methyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{2-oxo-1-[4-(trifluoromethyl)phenyl]propyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-[(4R)-7-(trifluoromethyl)-3,4-dihydro-1H-isochromen-4-yl]-1,6-dihydropyrimidine-4-carboxamide,

N-{cyano[4-(trifluoromethyl)phenyl]methyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{1-[4-(trifluoromethoxy)phenyl]cyclobutyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{1-[4-(trifluoromethyl)phenyl]cyclopentyl}-1,6-dihydropyrimidine-4-carboxamide,

N-{2-cyano-1-[4-(trifluoromethyl)phenyl]ethyl}-2-(dimethylamino)-6-oxo-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-[(1S)-6-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]-1,6-dihydropyrimidine-4-carboxamide,

methyl({[2-(dimethylamino)-6-oxo-1,6-dihydropyrimidin-4-yl]carbonyl}amino)[4-(trifluoromethyl)phenyl]acetate,

2-(dimethylamino)-6-oxo-N-{2,2,2-trifluoro-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide,

2-(dimethylamino)-6-oxo-N-{3-[4-(trifluoromethyl)phenyl]oxetan-3-yl}-1,6-dihydropyrimidine-4-carboxamide,

or a pharmaceutically acceptable salt thereof.

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