IP Library Granted Patent US 8,846,949
Granted Patent B2
US 8,846,949 · App. 13/968,476 · Granted Sep 30, 2014

Pyrrolopyrazoles as N-type calcium channel blockers

Inventors: Michael Winters (Morgantown, PA); Zhihua Sui (Piscataway, NJ)
Assignee: Janssen Pharmaceutica NV
C07D487/04
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Quick Facts
Patent No.
US 8,846,949
App. No.
13/968,476
Granted
Sep 30, 2014
Kind
B2
Abstract

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein R 1 , R 2 , R 3 , Q, and G are defined herein.

Claims (172)

1. A compound of Formula (I)

wherein

R 1 is selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, 2,2-difluoroethoxy, di(C 1-4 alkyl)amino, trifluoromethoxy, fluoro, and trifluoromethyl;

R 2 is hydrogen; or, R 2 may be taken with R 1 and the phenyl ring to which R 1 and R 2 are both attached to form 2,3-dihydrobenzofuran-7-yl or 1,3-benzodioxol-4-yl;

R 3 is hydrogen, methyl, methoxy, chloro, or fluoro;

Q is selected from the group consisting of Q1, Q2, and Q3;

wherein

R 4 is selected from the group consisting of hydrogen, C 1-4 alkyl, C 1-4 alkoxy, cyano, fluoro, and chloro;

R 5 is independently selected from the group consisting of hydrogen, C 1-4 alkyl, C 1-4 alkoxy, cyano, chloro, and di(C 1-4 alkyl)amino;

G is selected from the group consisting of 4-methylphenyl, 3-cyanophenyl, 4-cyanophenyl, 4-methoxycarbonylphenyl, 2-chloro-quinolin-6-yl, morpholin-4-ylsulfonyl, morpholin-4-yl(C 1-4 alkyl)aminosulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, C 6-10 aryl(C 1-4 alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, C 1-4 alkoxycarbonyl(C 1-4 )alkyl-sulfonyl, trifluoromethylsulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 alkyl-sulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 alkylsulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, methoxymethylcarbonyl, trifluoromethylcarbonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, C 1-4 alkoxycarbonylaminomethylcarbonyl, trifluoromethylsulfonylaminomethylcarbonyl, trifluoromethoxycarbonyl, C 1-4 alkylsulfonylaminomethyl-carbonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkoxycarbonyl, pyridinylcarbonyl, furanylcarbonyl, and 5-methylisoxazol-3-ylcarbonyl;

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

2. The compound of claim 1 wherein R 1 is selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, 2,2-difluoroethoxy, di(C 1-4 alkyl)amino, and trifluoromethoxy.

3. The compound of claim 2 wherein R 1 is selected from the group consisting of ethyl, methoxy, ethoxy, isopropyloxy, difluoroethoxy, dimethylamino, and trifluoromethoxy.

4. The compound of claim 1 wherein R 3 is hydrogen, methyl, chloro, or fluoro.

5. The compound of claim 1 wherein Q is selected from the group consisting of Q1, Q2, and Q3;

wherein

R 4 is chloro;

R 5 is independently selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, and chloro.

6. The compound of claim 5 wherein Q is selected from the group consisting of Q1, Q2, and Q3;

wherein

R 4 is chloro;

R 5 is independently selected from the group consisting of C 1-4 alkoxy and chloro.

7. The compound of claim 1 wherein G is selected from the group consisting of 4-methylphenyl, 2-chloro-quinolin-6-yl, C 6-10 aryl(C 1-4 )alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, trifluoromethylsulfonyl, C 1-4 alkoxycarbonyl(C 1-4 alkyl-sulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 alkylsulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 alkyl-sulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 )alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, morpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, methoxymethylcarbonyl, trifluoromethylcarbonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, C 1-4 alkoxycarbonylaminomethyl-carbonyl, C 1-4 alkylsulfonylaminomethyl-carbonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkoxycarbonyl, pyridinylcarbonyl, and furanylcarbonyl.

8. The compound of claim 7 wherein G is selected from the group consisting of methylphenyl, 2-chloro-quinolin-6-yl, C 6-10 aryl(C 1-4 )alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, 4-C 1-4 alkoxycarbonyl(C 1-4 )alkyl-sulfonyl, trifluoromethylsulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 )alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 )alkylsulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 )alkyl-sulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 )alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, morpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, methoxymethylcarbonyl, trifluoromethylcarbonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, C 1-4 alkoxycarbonylaminomethyl-carbonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkoxycarbonyl, and pyridinylcarbonyl.

9. The compound of claim 8 wherein G is selected from the group consisting of 2-chloro-quinolin-6-yl, C 6-10 aryl(C 1-4 )alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, C 1-4 alkoxycarbonyl(C 1-4 )alkyl-sulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 )alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 )alkylsulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 )alkyl-sulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 )alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, morpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, and C 1-4 alkoxycarbonyl.

10. The compound of Formula (I) as in claim 1

wherein

R 1 is selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, 2,2-difluoroethoxy, di(C 1-4 alkyl)amino, trifluoromethoxy, fluoro, and trifluoromethyl;

R 2 is hydrogen; or, R 2 may be taken with R 1 and the phenyl ring to which R 1 and R 2 are both attached to form 2,3-dihydrobenzofuran-7-yl or 1,3-benzodioxol-4-yl;

R 3 is hydrogen, methyl, methoxy, chloro, or fluoro;

Q is selected from the group consisting of Q1, Q2, and Q3;

wherein

R 4 is selected from the group consisting of chloro;

R 5 is independently selected from the group consisting of C 1-4 alkoxy and chloro;

G is selected from the group consisting of 4-methylphenyl, 2-chloroquinolin-6-yl, C 6-10 aryl(C 1-4 )alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, trifluoromethylsulfonyl, C 1-4 alkoxycarbonyl(C 1-4 )alkyl-sulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 -alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 )alkyl-sulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 )alkylsulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 )alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, morpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, methoxymethylcarbonyl, trifluoromethylcarbonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, C 1-4 alkoxycarbonylaminomethyl-carbonyl, C 1-4 alkylsulfonylaminomethyl-carbonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkoxycarbonyl, pyridinylcarbonyl, and furanylcarbonyl;

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

11. The compound of Formula (I) as in claim 1

wherein

R 1 is selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, 2,2-difluoroethoxy, di(C 1-4 alkyl)amino, trifluoromethoxy, fluoro, and trifluoromethyl;

R 2 is hydrogen; or, R 2 may be taken with R 1 and the phenyl ring to which R 1 and R 2 are both attached to form 2,3-dihydrobenzofuran-7-yl or 1,3-benzodioxol-4-yl;

R 3 is hydrogen, methyl, methoxy, chloro, or fluoro;

Q is selected from the group consisting of Q1, Q2, and Q3;

wherein

R 4 is chloro;

R 5 is independently selected from the group consisting of C 1-4 alkoxy and chloro;

G is selected from the group consisting of methylphenyl, 2-chloro-quinolin-6-yl, C 6-10 aryl(C 1-4 )alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, 4-C 1-4 alkoxycarbonyl(C 1-4 )alkyl-sulfonyl, trifluoromethylsulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 -alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 alkyl-sulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 alkyl-sulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, morpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, methoxymethylcarbonyl, trifluoromethylcarbonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, C 1-4 alkoxycarbonylaminomethyl-carbonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl)aminocarbonyl, C 1-4 alkoxycarbonyl, and pyridinylcarbonyl;

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

12. The compound of Formula (I) as in claim 1

wherein

R 1 is selected from the group consisting of ethyl, methoxy, ethoxy, isopropyloxy, difluoroethoxy, dimethylamino, and trifluoromethoxy;

R 2 is hydrogen; or, R 2 may be taken with R 1 and the phenyl ring to which R 1 and R 2 are both attached to form 2,3-dihydrobenzofuran-7-yl or 1,3-benzodioxol-4-yl;

R 3 is hydrogen, methyl, chloro, or fluoro;

Q is selected from the group consisting of Q1, Q2, and Q3;

wherein

R 4 is chloro;

R 5 is independently selected from the group consisting of C 1-4 alkoxy and chloro;

G is selected from the group consisting of 2-chloro-quinolin-6-yl, C 6-10 aryl(C 1-4 )alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, C 1-4 alkoxycarbonyl(C 1-4 alkyl-sulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 )alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 )alkylsulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 alkyl-sulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, morpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, and C 1-4 alkoxycarbonyl;

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

13. The compound of Formula (I) as in claim 1

wherein

R 1 is selected from the group consisting of ethyl, methoxy, ethoxy, isopropyloxy, difluoroethoxy, dimethylamino, and trifluoromethoxy;

R 2 is hydrogen;

R 3 is hydrogen, methyl, chloro, or fluoro;

Q is selected from the group consisting of Q1, Q2, and Q3;

wherein

R 4 is chloro;

R 5 is independently selected from the group consisting of C 1-4 alkoxy and chloro;

G is selected from the group consisting of 2-chloro-quinolin-6-yl, C 6-10 aryl(C 1-4 )alkylsulfonyl, C 6-10 aryloxy(C 1-4 )alkylsulfonyl, 3,5-dimethylisoxazol-4-yl-sulfonyl, C 1-4 alkoxycarbonyl(C 1-4 )alkyl-sulfonyl, C 3-7 cycloalkylsulfonyl, 2,2,2-trifluoroethylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, di(C 1-4 alkyl)aminosulfonylamino(C 1-4 alkyl-sulfonyl, C 1-4 alkylsulfonylamino(C 1-4 alkyl-sulfonyl, 2,5-dione-pyrrolidin-1-yl-(C 1-4 alkyl-sulfonyl, (2H)-1,3-dione-1H-isoindol-1-yl-(C 1-4 alkyl-sulfonyl, 1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl, C 1-6 alkylsulfonyl, di(C 1-4 alkyl)aminosulfonyl, pyrrolidin-1-ylsulfonyl, piperidin-1-ylsulfonyl, 4-(R 6 )-piperidin-1-ylsulfonyl wherein R 6 is C 1-4 alkoxycarbonyl or C 1-4 alkyl; azepan-1-ylsulfonyl, morpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl, C 1-4 alkoxycarbonylamino(C 2-4 )alkyl-carbonyl, and C 1-4 alkoxycarbonyl;

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

14. The compound of Formula (I) as in claim 1

selected from the group consisting of

tert-Butyl 3-(4-chlorophenyl)-2-(2-ethylphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-[(trifluoromethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-(pyridin-3-ylcarbonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-(pyridin-4-ylcarbonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-(trifluoroacetyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-(pyridin-2-ylcarbonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-(furan-2-ylcarbonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-[(5-methylisoxazol-3-yl)carbonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethylphenyl)-5-(methoxyacetyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

tert-Butyl{2-[3-(4-chlorophenyl)-2-(2-ethylphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]-2-oxoethyl}carbamate;

N-{2-[3-(4-Chlorophenyl)-2-(2-ethylphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]-2-oxoethyl}methanesulfonamide;

N-{2-[3-(4-Chlorophenyl)-2-(2-ethylphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]-2-oxoethyl}-1,1,1-trifluoromethanesulfonamide;

tert-Butyl 3-(4-chlorophenyl)-2-[2-(trifluoromethyl)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate;

3-(4-Chlorophenyl)-5-(methylsulfonyl)-2-[2-(trifluoromethyl)phenyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-[(1-methylethyl)sulfonyl]-2-[2-(trifluoromethyl)phenyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-[(4-methylphenyl)sulfonyl]-2-[2-(trifluoromethyl)phenyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

tert-Butyl{2-[3-(4-chlorophenyl)-2-[2-(trifluoromethyl)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]-2-oxoethyl}carbamate;

tert-Butyl 3-(4-chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate;

3-(4-Chlorophenyl)-5-(methylsulfonyl)-2-[2-(trifluoromethoxy)phenyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(trifluoroacetyl)-2-[2-(trifluoromethoxy)phenyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

tert-Butyl{2-[3-(4-chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5 (4H)-yl]-2-oxoethyl}carbamate;

3-[3-(4-Chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]benzonitrile;

Methyl 4-[3-(4-chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]benzoate;

4-[3-(4-Chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]benzonitrile;

4-[3-(4-Chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]-N-(2-morpholin-4-ylethyl)benzenesulfonamide;

2-Chloro-6-[3-(4-chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]quinoline;

tert-Butyl 3-(4-chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate;

tert-Butyl{2-[3-(4-chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5 (4H)-yl]-2-oxo ethyl}carbamate;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(cyclopropylsulfonyl)-2-(2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-N,N-dimethyl-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-N,N-dimethyl-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxamide;

3-(4-Chlorophenyl)-5-[(1-methylethyl)sulfonyl]-2-[2-(trifluoromethoxy)phenyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-[(2,2,2-trifluoroethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(cyclohexylsulfonyl)-2-(2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

2-(2-{[3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]sulfonyl}ethyl)-1H-isoindole-1,3(2H)-dione;

5-(Benzylsulfonyl)-3-(4-chlorophenyl)-2-(2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(cyclopentylsulfonyl)-2-(2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-[(1-methylbutyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

1-(2-{[3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]sulfonyl}ethyl)pyrrolidine-2,5-dione;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-[(2-phenoxyethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

N-(2-{[3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]sulfonyl}ethyl)methanesulfonamide;

N-(2-{[3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]sulfonyl}ethyl)propane-2-sulfonamide;

N′-(2-{[3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]sulfonyl}ethyl)-N,N-dimethylsulfamide;

Methyl 3-{[3-(4-chlorophenyl)-2-[2-(trifluoromethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]sulfonyl}propanoate;

3-(4-Chlorophenyl)-5-[(1,1-dioxidotetrahydrothiophen-3-yl)sulfonyl]-2-[2-(trifluoromethoxy)phenyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethoxyphenyl)-5-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethoxyphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(cyclopentylsulfonyl)-2-(2-ethoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(cyclohexylsulfonyl)-2-(2-ethoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

5-(Benzylsulfonyl)-3-(4-chlorophenyl)-2-(2-ethoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-ethoxyphenyl)-N,N-dimethyl-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

5-(Azepan-1-ylsulfonyl)-3-(4-chlorophenyl)-2-(2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-N,N-diethyl-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-[(4-methylpiperidin-1-yl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

Methyl 1-{[3-(4-chlorophenyl)-2-(2-methoxyphenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]sulfonyl}piperidine-4-carboxylate;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-(morpholin-4-ylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-(pyrrolidin-1-ylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-{[(2S,6S)-2,6-dimethylmorpholin-4-yl]sulfonyl}-2-(2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxyphenyl)-5-(piperidin-1-ylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-N,N-dimethyl-2-[2-(1-methylethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

2-(4-Chloro-2-methoxyphenyl)-3-(4-chlorophenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

2-(4-Chloro-2-methoxyphenyl)-3-(4-chlorophenyl)-N,N-dimethyl-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

3-(4-Chlorophenyl)-2-(4-methoxy-2-methylphenyl)-5-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(4-methoxy-2-methylphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(cyclohexylsulfonyl)-2-(4-methoxy-2-methylphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(4-methoxy-2-methylphenyl)-N,N-dimethyl-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

3-(4-Chlorophenyl)-2-(4-fluoro-2-methoxyphenyl)-5-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(4-fluoro-2-methoxyphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-5-(cyclohexylsulfonyl)-2-(4-fluoro-2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(4-fluoro-2-methoxyphenyl)-5-[(4-methylpiperidin-1-yl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxy-4-methylphenyl)-5-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxy-4-methylphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxy-4-methylphenyl)-5-[(1-methylbutyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-methoxy-4-methylphenyl)-5-[(4-methylpiperidin-1-yl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-fluoro-4-methoxyphenyl)-5-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-fluoro-4-methoxyphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2-fluoro-4-methoxyphenyl)-5-[(4-methylpiperidin-1-yl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

2-(1,3-Benzodioxol-4-yl)-3-(4-chlorophenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

2-(1,3-Benzodioxol-4-yl)-3-(4-chlorophenyl)-5-[(2-methylpropyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

2-(1,3-Benzodioxol-4-yl)-3-(4-chlorophenyl)-5-[(4-methylpiperidin-1-yl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2,3-dihydro-1-benzofuran-7-yl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2,3-dihydro-1-benzofuran-7-yl)-5-[(2-methylpropyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-(2,3-dihydro-1-benzofuran-7-yl)-5-[(4-methylpiperidin-1-yl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole

3-(4-Chlorophenyl)-5-[(3,5-dimethylisoxazol-4-yl)sulfonyl]-2-(2-methoxyphenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

2-[3-(4-Chlorophenyl)-5-[(1-methylethyl)sulfonyl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl]-N,N-dimethylaniline;

2-[3-(4-Chlorophenyl)-5-(ethylsulfonyl)-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl]-N,N-dimethylaniline;

3-(4-Chlorophenyl)-N,N-dimethyl-2-[2-(2,2,2-trifluoroethoxy)phenyl]-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

2-(2-tert-Butoxyphenyl)-3-(4-chlorophenyl)-N,N-dimethyl-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

3-(6-Chloropyridin-3-yl)-2-(2-methoxyphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-{2-(2-Methoxyphenyl)-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl}quinoline;

2-(2-Methoxyphenyl)-5-[(1-methylethyl)sulfonyl]-3-(6-methylpyridin-3-yl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

3-(4-Chlorophenyl)-2-[2-(2,2-difluoroethoxy)phenyl]-N,N-dimethyl-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide;

2-(2-Methoxyphenyl)-3-[6-(1-methylethoxy)pyridin-3-yl]-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

2-(2-Methoxyphenyl)-3-(6-methoxypyridin-3-O-5-[(1-methylethyl)sulfonyl]-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole;

or a pharmaceutically acceptable salt form thereof.

15. A pharmaceutical composition comprising a compound of claim 1 or 14 and at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and a pharmaceutically acceptable diluent.

16. A pharmaceutical composition of claim 15 , wherein the composition is a solid oral dosage form.

17. A pharmaceutical composition of claim 15 , wherein the composition is a syrup, an elixir or a suspension.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2015
From: SUI, ZHIHUA
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 035645/0690 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 22, 2014
From: WINTERS, MICHAEL
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 033588/0347 →
Continuity (2)
Provisional Application 61683780 · Aug 16, 2012
Related Publication 20140051688A1 · Feb 20, 2014