IP Library Granted Patent US 10,160,762
Granted Patent B2
US 10,160,762 · App. 15/574,411 · Granted Dec 25, 2018

6-alkyl dihydropyrazolopyrimidinone compounds as PDE2 inhibitors

Inventors: Dong-Ming Shen (Edison, NJ); Michael P. Dwyer (Scotch Plains, NJ); Christopher J. Sinz (South San Francisco, CA); Deping Wang (Furlong, PA); Shawn J. Stachel (Perkasie, PA); Daniel V. Paone (Lansdale, PA); Ashley Forster (Harleysville, PA); Richard Berger (Harleysville, PA); Yili Chen (Hillsborough, NJ); Yimin Qian (Plainsboro, NJ); Shimin Xu (Beijing, CN); Chunmei Hu (Beijing, CN); William D. Shipe (Chalfont, PA); Jianmin Fu (Beijing, CN); Zhigang Guo (Beijing, CN); Haitang Li (Beijing, CN); Yingjian Bo (Beijing, CN)
Assignee: Merck Sharp & Dohme Corp.
C07D487/04A61K31/519A61P25/00A61P25/14A61P25/16A61P25/18A61P25/28
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Quick Facts
Patent No.
US 10,160,762
App. No.
15/574,411
Granted
Dec 25, 2018
Kind
B2
Abstract

The present invention is directed to 6-alkyl dihydropyrazolopyrimidinone compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypo-function or basal ganglia dysfunction.

Claims (365)

1. A compound represented by structural formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X represents ZC 6-10 aryl, said aryl optionally substituted with 1 to 3 groups of R a ;

Z represents a bond, —(CH2) n -, —(C(O)NH—, —CH(OH)—, —C(CH 3 )OH—, —(CH 2 ) n NH—, or —(CH 2 ) n NCH 3 —;

R 1 represents C 1-6 alkyl, (CH 2 ) 1-4 OR, C 1-4 haloalkyl, wherein said alkyl, are optionally substituted with 1 to 3 groups of R a ;

R 2 represents halo, C 1-6 alkyl, (CH 2 ) n OR, or C 1-4 haloalkyl, said alkyl optionally substituted with 1 to 3 groups of R a ,

R 3 and R 3a independently represent hydrogen, C 1-6 alkyl, or C 3-6 cycloalkyl, or R 3 and

R 3a can combine with the carbon atom to which they are attached to form a C 3-6 cycloalkyl, said alkyl, and cycloalkyl, optionally substituted with 1 to 3 groups of R a ,

R represents hydrogen or C 1-6 alkyl, said alkyl optionally substituted with 1 to 3 groups of R a ,

R a is selected from the group consisting of halo, CN, C 1-6 alkyl, (CH 2 ) n OR, (CH 2 ) n C 1-4 haloalkyl, O—C 1-4 haloalkyl, SCF 3 , SF 5 , C 6-10 aryl, C(O)N(CH 3 ) 2 , NHOH, SO 2 R, NR 2 , OC(O)CH 3 , NHC(O)CH 3 , OCH 2 C 6-10 aryl, and C 3-6 cycloalkyl, said cycloalkyl optionally substituted with 1 to 3 groups selected from C 1-6 alkyl and C 1-4 haloalkyl;

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

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein Z is a bond.

3. The compound according claim 2 or a pharmaceutically acceptable salt thereof wherein X is optionally substituted phenyl.

4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from the group consisting of CH 3 , (CH2) 2 CH 3 , CH 2 (CH 3 ) 2 , CH 2 C(CH 3 ) 3 , (CH 2 ) n OCH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH(CH 3 )OH, (CH 2 ) 2 OCH 2 CH 3 , CHF 2 , CF 3 , and CH 2 F.

5. The compound according to claim 4 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from the group consisting of CH 3 , (CH2) 2 CH 3 , CH 2 (CH 3 ) 2 , CH 2 C(CH 3 ) 3 , (CH 2 ) n OCH 3 , CH 2 CH 3 , and CH(CH 3 ) 2 .

6. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R 2 is selected from the group consisting of optionally substituted CH 2 OH, CH 3 , CH 2 CN, CH(CH 3 )OH, C(CH 3 ) 2 OH, CH 2 NHC(O)CH 3 , CH 2 C(CH 3 )OH, CH 2 OC(O)CH 3 , CH 2 SO 2 CH 3 , CH 2 NHOH, CH 2 F, CHF 2 , (CH 2 ) n CF 3 , CH(CF 3 )OH, CF 2 CH 2 OH, C(CH 3 )CH 2 OH, and CH 2 oxetanyl.

7. The compound according to claim 6 or a pharmaceutically acceptable salt thereof wherein R 2 is selected from the group consisting of optionally substituted CH 2 OH, CH 3 , CH 2 F, CHF 2 , (CH 2 ) n CF 3 , and CF 2 CH 2 OH.

8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein each R 3 and R 3a independently represents hydrogen, CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 , CH 2 OCH 3 , C(CH 3 ) 3 , CH 2 CF 3 , and optionally substituted cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

9. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein one of R 3 and R 3a is hydrogen and the other is selected from the group consisting of CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 , CH2OCH3, C(CH 3 ) 3 , CH 2 CF 3 , and optionally substituted cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

10. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein one of R 3 and R 3a is hydrogen and the other is CH 3 , CH(CH 3 ) 2 or optionally substituted cyclopropyl.

11. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R 3 and R 3a combine with the carbon atom to which they are attached to form oxetanyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

12. The compound according to claim 1 or a pharmaceutically acceptable salt thereof represented by structural formula Ia:

wherein R 1 , R 2 , R 3 , R 3a and R a are as originally described.

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

or a pharmaceutically acceptable salt thereof wherein R 2 is selected from the group consisting of optionally substituted CH 2 OH, CH 3 , CH 2 CN, CH(CH 3 )OH, C(CH 3 ) 2 OH, CH 2 NHC(O)CH 3 , CH 2 C(CH 3 )OH, CH 2 OC(O)CH 3 , CH 2 SO 2 CH 3 , CH 2 NHOH, and CH 2 OCH 2 phenyl, CH 2 F, CHF 2 , (CH 2 ) n CF 3 , CF 2 CH 2 OH, C(CH 3 )CH 2 OH, CH(CF 3 ), and CH 2 oxetanyl, R 3 and R 3a independently represents hydrogen, CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 , CH 2 OCH3, C(CH 3 ) 3 , CH 2 CF 3 , and optionally substituted cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl or R 3 and R 3a combine with the carbon atom to which they are attached to form oxetanyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and the R a on the phenyl ring of formula Ib is selected from fluorine, chlorine, iodine, bromine, CH 3 , CH(CH 3 ) 2 , C(CH 3 ) 3 , (CH 2 ) n OCH 3 , OC(CH 3 ) 2 , C(CH 3 )F 2 , CF 2 CF 3 , CH 2 F, CHF 2 , CF 3 , OCHF 2 , OCF 3 , SF 5 , and optionally substituted cyclopropyl.

14. The compound according to claim 13 or a pharmaceutically acceptable salt thereof wherein the invention of formula Ib is realized when R 2 is CH 2 OH, CH 2 F, CHF 2 or CH 3 , one of R 3 and R 3a is hydrogen and the other is selected from the group consisting of CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 , C(CH 3 ) 3 , CH 2 CF 3 , and cyclopropyl, or R 3 and R 3a combine with the carbon atom to which they are attached to form an optionally substituted C 3-6 cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and the R a on the phenyl ring of formula Ia is selected from fluorine, iodine, CH 3 , CH(CH 3 ) 2 , C(CH 3 ) 3 , (CH 2 ) n OCH 3 , OC(CH 3 ) 2 , C(CH 3 )F 2 , CF 2 CF 3 , CH 2 F, CHF 2 , CF 3 , OCHF 2 , OCF 3 , SF 5 , and cyclopropyl.

15. A compound which is:

1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-(1-p-tolylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

1-(1-(4-Cyclopropylphenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-(2-methyl-1-(4-(trifluoromethyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-(2,2,2-trifluoro-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-[4-(trifluoromethyl)benzyl]-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-(Hydroxymethyl)-6-methyl-1-{1-methyl-1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-1-(1-(3-Fluoro-4-(trifluoromethoxy)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(3-Fluoro-4-(trifluoromethoxy)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-((3-Fluoro-4-(trifluoromethyl)phenyl)(1-methylcyclopropyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-((3-Fluoro-4-(trifluoromethyl)phenyl)(1-methylcyclopropyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(2-Fluoro-4-(trifluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(2-Fluoro-4-(trifluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(2-Chloro-4-(trifluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(2-Chloro-4-(trifluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-(Difluoromethoxy)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-(Difluoromethoxy)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoromethylthio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoromethylthio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-((1-methylcyclopropyl)(4-(trifluoromethyl)phenyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-((1-methylcyclopropyl)(4-(trifluoromethyl)phenyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

1-(Cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-(1-Hydroxyethyl)-3-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-(3-Hydroxybenzyl)-3-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-(2-Hydroxybenzyl)-3-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

N,N-Dimethyl-3-(3-methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)propanamide,

3-Methyl-6-(tetrahydrofuran-3-yl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-(2-Methoxyethyl)-3-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-(2-Ethoxyethyl)-3-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3,6-Dimethyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3,6-Dimethyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1, 5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-Ethyl-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-Cyclobutyl-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-Cyclopentyl-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-Methyl-6-propyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-Cyclopropyl-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-Methyl-6-(1-methylethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-(3,4-Dimethoxybenzyl)-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-(3-Methoxybenzyl)-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-(4-Methoxybenzyl)-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-(3-Methoxyphenyl)-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-(Methoxymethyl)-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

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

3-Methyl-6-quinoxalin-2-yl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-(Fluoromethyl)-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-Methyl-6-pyridin-2-yl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

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

6-(2,5-Dimethyl-1,3-oxazol-4-yl)-3-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-Methyl-6-(tetrahydro-2H-pyran-4-yl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-1-(2,2-Dimethyl-1-(4-(trifluoromethyl)phenyl)propyl)-6-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(2,2-Dimethyl-1-(4-(trifluoromethyl)phenyl)propyl)-6-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-1-((1-methylcyclopropyl)(4-(trifluoromethyl)phenyl)methyl)-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-1-((1-methylcyclopropyl)(4-(trifluoromethyl)phenyl)methyl)-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-2,2-dimethylpropyl)-6-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-2,2-dimethylpropyl)-6-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-((3-Fluoro-4-(trifluoromethyl)phenyl)(1-methylcyclopropyl)methyl)-6-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-((3-Fluoro-4-(trifluoromethyl)phenyl)(1-methylcyclopropyl)methyl)-6-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-3-(2,2,2-trifluoroethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(2,2,2-trifluoroethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-3-(2,2,2-trifluoroethyl)-1-(1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(2,2,2-trifluoroethyl)-1-(1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-3-(trifluoromethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(trifluoromethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R, R)-6-Methyl-3-(-tetrahydrofuran-2-yl)-1-(-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R, S)-6-Methyl-3-(-tetrahydrofuran-2-yl)-1-(-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S, R)-6-Methyl-3-(-tetrahydrofuran-2-yl)-1-(-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S, S)-6-Methyl-3-(-tetrahydrofuran-2-yl)-1-(-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Furan-2-yl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Furan-2-yl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)cyclobutyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Hydroxymethyl)-6-methyl-1-(3-(4-(trifluoromethyl)phenyl)oxetan-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(2,2-Dimethyl-1-(4-(trifluoromethyl)phenyl)-propyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(2,2-Dimethyl-1-(4-(trifluoromethyl)phenyl)-propyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(2-methyl-1-(4-(trifluoromethoxy)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(2-methyl-1-(4-(trifluoromethoxy)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-2-methylpropyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-2-methylpropyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-((4-tert-Butylphenyl)(cyclopropyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-((4-tert-Butylphenyl)(cyclopropyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(Cyclopropyl(4-(trifluoromethoxy)phenyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(Cyclopropyl(4-(trifluoromethoxy)phenyl)methyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(3,3,3-trifluoro-1-(4-(trifluoromethyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(3,3,3-trifluoro-1-(4-(trifluoromethyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(perfluoroethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(perfluoroethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-1-(2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-1-(2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(5-(trifluoromethyl)-2, 3-dihydro-1H-inden-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(2-Fluoro-4-(trifluoromethoxy)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(2-Fluoro-4-(trifluoromethoxy)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(3-methyl-4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(3-methyl-4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(2-methyl-4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(2-methyl-4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-(Difluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-(Difluoromethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-(Difluoromethoxy)-3-fluorophenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-(Difluoromethoxy)-3-fluorophenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-(1,1-Difluoroethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-(1,1-Difluoroethyl)phenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-(Difluoromethoxy)-2-fluorophenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-(Difluoromethoxy)-2-fluorophenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(2,2,2-trifluoroethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(2,2,2-trifluoroethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-((trans)-4-(trifluoromethyl)cyclohexyl)ethyl)-1H-pyrazolo[3,4-d]-pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-((trans)-4-(trifluoro-methyl)cyclohexyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methylpropyl)-3-(hydroxyl-methyl)-6-methyl-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methylpropyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-2,2-dimethylpropyl)-3-(hydroxyl-methyl)-6-methyl-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-2,2-dimethylpropyl)-3-(hydroxyl-methyl)-6-methyl-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(6-(trifluoro-methyl)pyridin-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoro-methyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoro-methyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoro-methoxy)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoro-methoxy)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(2,6-Difluoro-4-(trifluoromethyl)phenyl)-ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(2,6-Difluoro-4-(trifluoromethyl)phenyl)-ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-1-(1-(3-iodo-4-(trifluoromethyl-)phenyl)ethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-(Hydroxymethyl)-1-(1-(3-iodo-4-(trifluoromethyl-)phenyl)ethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-3-(Hydroxymethyl)-1-(1-(2-iodo-4-(trifluoromethyl-)phenyl)ethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-(Hydroxymethyl)-1-(1-(2-iodo-4-(trifluoromethyl-)phenyl)ethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)cyclopropyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(1-methylcyclopropyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(1-methylcyclopropyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(6-(trifluoromethyl)pyridazin-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(6-(trifluoromethyl)pyridazin-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(5-Chlorothiophen-2-yl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(5-Chlorothiophen-2-yl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-methyl-1-(1-(5-(trifluoromethyl)thiophen-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(5-(trifluoromethyl)thiophen-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-tert-Butylphenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-methyl-1-(1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-tert-Butylphenyl)-2-methylpropyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-tert-Butylphenyl)-2-methylpropyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Difluoromethyl)-6-methyl-1-(3-(4-(trifluoromethyl)phenyl)oxetan-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Difluoromethyl)-6-methyl-1-(1-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Difluoromethyl)-6-methyl-1-(1-(4-(perfluoroethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Difluoromethyl)-6-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-3-(Difluoromethyl)-1-(1-(3-fluoro-4-(trifluoromethyl)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-1-(1-(3-fluoro-4-(trifluoromethyl)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-1-(1-(3-fluoro-4-(trifluoromethoxy)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-1-(1-(3-fluoro-4-(trifluoromethoxy)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-methyl-1-(2-methyl-1-(4-(trifluoromethyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-6-methyl-1-(2-methyl-1-(4-(trifluoromethyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-on,

(R)-3-(Difluoromethyl)-1-(2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-1-(2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(trifluoromethylthio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-6-methyl-1-(1-(4-(trifluoromethylthio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-(Difluoromethoxy)phenyl)ethyl)-3-(difluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-(Difluoromethoxy)phenyl)ethyl)-3-(difluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(2-Chloro-4-(trifluoromethyl)phenyl)ethyl)-3-(difluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(2-Chloro-4-(trifluoro-methyl)phenyl)-ethyl)-3-(difluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoro-methyl)-1-(1-(2-fluoro-4-(trifluoro-methyl)phenyl)-ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoro-methyl)-1-(1-(2-fluoro-4-(trifluoromethyl)phenyl)ethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-(methoxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo-[3,4-d]pyrimidin-4-one,

(S)-3-(Difluoro-methyl)-6-(methoxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo-[3,4-d]pyrimidin-4-one,

(R)-3-(Difluoromethyl)-6-ethyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-(Difluoromethyl)-6-ethyl-1-(1-(4-(trifluoromethyl)-phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-6-Cyclopropyl-3-(difluoromethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-Cyclopropyl-3-(difluoromethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

1-(Cyclopropyl(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-3-(difluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-methyl-1-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-6-methyl-1-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Difluoromethyl)-6-(3,4-dimethoxybenzyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Difluoromethyl)-6-(3,4-dimethoxybenzyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Difluoromethyl)-6-(3,4-dimethoxybenzoyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Fluoromethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Fluoromethyl)-6-methyl-1-(1-(4-(pentafluorothio)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Fluoromethyl)-6-methyl-1-(2,2,2-trifluoro-1-(4-(trifluoromethyl)phenyl)-ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Fluoromethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)cyclobutyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Fluoromethyl)-6-methyl-1-(1-p-tolylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Fluoromethyl)-6-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-(Fluoromethyl)-6-(methoxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-3-(Fluoromethyl)-6-methyl-1-(1-(4-(trifluoro-methoxy-)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Fluoromethyl)-6-methyl-1-(1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Fluoromethyl)-6-methyl-1-((1-methylcyclopropyl)(4-(trifluoromethyl)phenyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Fluoromethyl)-6-methyl-1-((1-methylcyclopropyl)(4-(trifluoromethyl)phenyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Fluoromethyl)-6-methyl-1-(1-(4-(2,2,2-trifluoroethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Fluoromethyl)-6-methyl-1-(1-(4-(2,2,2-trifluoroethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Fluoromethyl)-6-methyl-1-(2-methyl-1-(4-(trifluoromethyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Fluoromethyl)-6-methyl-1-(2-methyl-1-(4-(trifluoromethyl)phenyl)propyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-tert-Butylphenyl)ethyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-tert-Butylphenyl)ethyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(3-Fluoro-4-(trifluoromethoxy)phenyl)ethyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(3-Fluoro-4-(trifluoromethoxy)phenyl)ethyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Fluoromethyl)-6-(4-methoxybenzyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Fluoromethyl)-6-(4-methoxybenzyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Fluoromethyl)-6-(3-methoxybenzyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Fluoromethyl)-6-(3-methoxybenzyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-(3,4-Dimethoxybenzyl)-3-(fluoromethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-(3,4-Dimethoxybenzyl)-3-(fluoromethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-1-(Cyclopropyl(4-(trifluoromethoxy)phenyl)methyl)-3-(fluoromethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-1-(Cyclopropyl(4-(trifluoromethoxy)phenyl)methyl)-3-(fluoromethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-(fluoromethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-(fluoromethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-3-(fluoromethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-1-(Cyclopropyl(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-3-(fluoromethyl)-6-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

1-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)ethyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

1-(Cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(Chloromethyl)-1-(cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(2,2-Dimethyl-1-(4-(trifluoromethyl)phenyl)propyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(2,2-Dimethyl-1-(4-(trifluoromethyl)phenyl)propyl)-3-(fluoromethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-3-(1H-pyrazol-5-yl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(1H-pyrazol-5-yl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-3-(1H-pyrazol-4-yl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(1H-pyrazol-4-yl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-Methyl-3-((R)-3,3,3-trifluoro-2-hydroxypropyl)-1-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-Methyl-3-((S)-3,3,3-trifluoro-2-hydroxypropyl)-1-((S)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-Methyl-3-((R)-3,3,3-trifluoro-2-hydroxypropyl)-1-((S)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-Methyl-3-((S)-3,3,3-trifluoro-2-hydroxypropyl)-1-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-((R)-2-Hydroxypropyl)-6-methyl-1-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-((S)-2-hydroxypropyl)-6-methyl-1-((S)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-((R)-2-hydroxypropyl)-6-methyl-1-((S)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-((S)-2-hydroxypropyl)-6-methyl-1-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-(2-Hydroxy-2-methylpropyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carbaldehyde,

(R)-3-(2-Hydroxyethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(2-Hydroxyethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(Z)-6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carbaldehyde oxime,

(S)-6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carbonitrile,

(S)-6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carbonitrile,

(R)-3-(1,1-Difluoro-2-hydroxyethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(1,1-Difluoro-2-hydroxyethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(S)-6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

3-Amino-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-N-(6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)acetamide,

(S)-N-(6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)acetamide,

N-(6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)methanesulfonamide,

(R)-6-Methyl-3-(1,3,4-oxadiazol-2-yl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(1,3,4-oxadiazol-2-yl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-N,6-Dimethyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(S)-N,6-Dimethyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(R)-N,N,6-Trimethyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(S)-N,N,6-Trimethyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(R)-6-Methyl-4-oxo-N-(2,2,2-trifluoroethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(S)-6-Methyl-4-oxo-N-(2,2,2-trifluoroethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide,

(R)-6-Methyl-3-(morpholine-4-carbonyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(morpholine-4-carbonyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-3-(methyl sulfonylmethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-6-Methyl-3-(methyl sulfonylmethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Aminomethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Aminomethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-N-((6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)methyl)acetamide,

(S)-N-((6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)methyl)acetamide,

(R)-3-(Methoxymethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Methoxymethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-2-(6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)acetonitrile,

(S)-2-(6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)acetonitrile,

3-(2-Aminoethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3-((Benzyloxy)methyl)-6-(difluoromethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-(Difluoromethyl)-3-(hydroxymethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(2,2-Difluoroethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(2,2-Difluoroethyl)-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-6-Methyl-3-(2,2,2-trifluoroethoxy)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

and (S)-6-Methyl-3-(2,2,2-trifluoroethoxy)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-Methyl-3-(oxetan-3-ylmethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-1-(1-(4-Acetylphenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-1-(1-(4-Acetylphenyl)ethyl)-3-(hydroxymethyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(R)-3-(Hydroxymethyl)-6-(methoxymethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

(S)-3-(Hydroxymethyl)-6-(methoxymethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

6-Furan-2-yl-3-(hydroxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-(Hydroxymethyl)-6-(1-methylethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-(3,4-Dimethoxybenzyl)-3-(hydroxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-(Hydroxymethyl)-6-[(5-methyltetrahydrofuran-2-yl)methyl]-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-6-Cyclopropyl-3-(hydroxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-Cyclopropyl-3-(hydroxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-6-Ethyl-3-(hydroxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-Ethyl-3-(hydroxymethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-3-(Hydroxymethyl)-6-propyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-(Hydroxymethyl)-6-propyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-3-(Hydroxy-methyl)-6-isobutyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo-[3,4-d]pyrimidin-4-one,

(S)-3-(Hydroxy-methyl)-6-isobutyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-6-(Cyclopentyl-methyl)-3-(hydroxymethyl)-1-(1-(4-(trifluoromethyl)-phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-(Cyclopentyl-methyl)-3-(hydroxymethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-6-(Cyclopropyl-methyl)-3-(hydroxymethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-(Cyclopropyl-methyl)-3-(hydroxymethyl)-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R,R)-3-(Hydroxymethyl)-6-(tetrahydrofuran-2-yl)-1-(1-(4-(trifluoromethyl)-phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S,S)-3-(Hydroxymethyl)-6-(tetrahydrofuran-2-yl)-1-(1-(4-(trifluoromethyl-)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R,S)-3-(Hydroxymethyl)-6-(tetrahydrofuran-2-yl)-1-(1-(4-(trifluoromethyl)-phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S,R)-3-(Hydroxymethyl)-6-(tetrahydrofuran-2-yl)-1-(1-(4-(trifluoromethyl)-phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-6-Cyclopropyl-3-(hydroxymethyl)-1-{1-[4-(pentafluoro-sulfanyl)-phenyl]-ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-Cyclopropyl-3-(hydroxymethyl)-1-{1-[4-(pentafluoro-sulfanyl)-phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(R)-3-(Hydroxy-methyl)-6-(methoxy-methyl)-1-{1-[4-(pentafluoro-sulfanyl)-phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-(Hydroxymethyl)-6-(methoxymethyl)-1-{1-[4-(pentafluorosulfanyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)methyl acetate,

3-((R)-1-Hydroxypropan-2-yl)-6-methyl-1-((S)-1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-((S)-1-Hydroxypropan-2-yl)-6-methyl-1-((S)-1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-Acetyl-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-6-Methyl-4-oxo-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid,

(R)-3-Bromo-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-Bromo-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-(1-Hydroxy-1-methylethyl)-6-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

6-Methyl-3-(2,2,2-trifluoro-1-hydroxyethyl)-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3-(1-Hydroxyethyl)-6-methyl-1-{1-[4-(trifluoromethyl)phenyl]ethyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

(S)-3-Hydroxy-6-methyl-1-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

3,6-Dimethyl-1-(1-(4-(trifluoromethyl)phenylamino)propan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

3,6-Dimethyl-1-(1-(methyl(4-(trifluoromethyl)phenyl)amino)propan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

1-(1-Hydroxy-1-(4-(trifluoromethyl)phenyl)propan-2-yl)-3,6-dimethyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

2-(3,6-Dimethyl-4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidin-1-yl)-N-(4-(trifluoromethyl)phenyl)propanamide,

1-(2-Hydroxy-2-(4-(trifluoromethyl)phenyl)propyl)-3,6-dimethyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one,

1-(1-ethyl-4-phenylbutyl)-3,6-dimethyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

1-[1-(2,4-dimethyl-1,3-thiazol-5-yl)-4-phenylbutyl]-3,6-dimethyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,

or a pharmaceutically acceptable salt thereof.

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

17. A compound of claim 1 or a pharmaceutically acceptable salt thereof for use in medicine.

Assignments (5)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2017
From: QIAN, YIMIN
To: MSD R & D (CHINA) CO. LTD.
Reel/Frame 044174/0943 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2017
From: SHEN, DONG MING; SINZ, CHRISTOPHER J.; DWYER, MICHAEL P.; CHEN, YILI; PAONE, DANIEL V.; WANG, DEPING; STACHEL, SHAWN J.; FORSTER, ASHLEY; SHIPE, WILLIAM D.; BERGER, RICHARD
To: MERCK SHARP & DOHME CORP.
Reel/Frame 044176/0215 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2017
From: XU, SHIMIN; HU, CHUNMEI; GUO, ZHIGANG; FU, JIANMIN; LI, HAITANG; BO, YINGJIAN
To: PHARMARON BEIJING CO. LTD.
Reel/Frame 044176/0633 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2017
From: PHARMARON BEIJING CO. LTD.
To: MERCK SHARP & DOHME CORP.
Reel/Frame 044176/0813 →
Priority Claims (1)
WO PCT/CN2015/080267 · May 29, 2015 · international
Continuity (1)
Related Publication 20180134712A1 · May 17, 2018