IP Library › Granted Patent US 10,144,732
Granted Patent B2
US 10,144,732 · App. 15/316,534 · Granted Dec 4, 2018

ATX modulating agents

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,144,732
App. No.
15/316,534
Granted
Dec 4, 2018
Kind
B2
Abstract

Compounds of formula (I) can modulate the activity of autotaxin (ATX).

Claims (367)

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

X is selected from —C(O)—, —C(O) 2 —, and —C(O)NR X —;

Z is a bond or C 1-5 alkylene;

Ring A is selected from cyclohexyl, phenyl, and 5- or 6-membered heteroaryl, wherein Ring A is optionally substituted with one to three R 1 ;

R 1 is selected from C 1-4 alkyl, halo, —CN, —OR 1a , —S(O) 2 R 1a , —C(O) 2 R 1a , —NO 2 , —N(R 1a )C(O) 2 R 1a , —N(R 1a )S(O) 2 R 1a , and —SR 1a , wherein said C 1-4 alkyl is optionally substituted with one to three R 10 ;

R 1a in each occurrence is independently selected from H and C 1-4 alkyl;

R 10 in each occurrence is independently selected from halo, —OR 10a , and —N(R 10a ); and

R 10a in each occurrence is independently selected from H and C 1-4 alkyl;

R L is selected from H and C 1-3 alkyl;

R X is selected from H and C 1-3 alkyl;

R 2 is H, halo or C 1-4 alkyl optionally substituted with 1 to 3 halo;

R 3 is selected from:

i. —[CHR 3a ] z —R 4 ;

ii. —[CHR 3a ] x -L-[CHR 3a ] y —R 4 ;

iii. —[CHR 3a ] z -(L) m -R 5 ;

iv. —[CHR 3a ] x -L-[CHR 3a ] y —R 5 ; and

v. R 5 ,

m is 0 or 1;

L is selected from —N(R L )— and —O—;

R 3a is hydrogen or C 1-3 alkyl;

x and y are each independently selected from 1, 2, or 3;

z is 1, 2, 3, 4, 5, or 6;

R 4 is selected from —C(O) 2 R 4a , —C(O)N(R 4a ) 2 , —OR 4a , —N(R 4a ) 2 , CN, —S(O) 2 N(R 4a ) 2 , —S(O) 2 N(R 4a )C(O)R 4a , —SR 4a , —S(O)R 4a , —S(O) 2 R 4a , —S(O) 2 OR 4a , —C(O)N(R 4a) S(O) 2 R 4a , —C(O)N(R 4a )S(O) 2 R 4a , —C(O)N(R 4a )OR 4a , —C(O)N(R 4a )CN, —CR 4a (CF 3 )OR 4a , —C(CF 3 ) 2 OR 4a , —P(O)(OR 4a ) 2 , and —B(OR 4a ) 2 ;

R 4a in each occurrence is independently selected from H and C 1-6 alkyl;

R 5 is selected from 3- to 12-membered carbocyclyl and 3- to 12-membered heterocyclyl, wherein R 5 is optionally substituted with one or more R 30 ;

R 30 in each occurrence is independently selected from 3- to 6-membered monocyclic carbocyclyl, 3- to 6-membered monocyclic heterocyclyl, C 1-6 alkyl, halo, CN, —S(O) 2 OR 30a , —S(O) 2 N(R 30a ) 2 , —S(O) 2 N(R 30a )C(O)R 30a , —C(O)N(R 30a )S(O) 2 R 30a , —C(O)N(R 30a )S(O) 2 R 30a , —C(O)N(R 30a )OR 30a , —C(O)N(R 30a )CN, —CH(CF 3 )OR 30a , —C(CF 3 ) 2 OR 30a , —P(O)(OR 30a ) 2 , —B(OR 30a ) 2 , —C(O) 2 R 30a , —C(O)N(R 30a ) 2 , —OR 30a , —N(R 30a ) 2 , and —C(O)R 30a , wherein said 3- to 6-membered monocyclic carbocyclyl, 3- to 6-membered monocyclic heterocyclyl, and C 1-6 alkyl in each occurrence are optionally and independently substituted with one or more R 35 ; and

R 30a in each occurrence is independently selected from H, C 1-6 alkyl, 3- to 6-membered monocyclic carbocyclyl, and 3- to 6-membered monocyclic heterocyclyl;

R 35 in each occurrence is independently selected from halo, —OR 35a , —C(O) 2 R 35a , —C(O)N(R 35a ) 2 , —S(O) 2 R 30a , and —N(R 35a ) 2 ; and

R 35a in each occurrence is independently selected from H and C 1-6 alkyl.

2. The compound of claim 1 , wherein the compound is represented by the following formula:

or a pharmaceutically acceptable salt thereof, wherein R x is hydrogen or methyl; n is 0, 1, or 2.

3. The compound of claim 2 , wherein Ring A is either unsubstituted or substituted with 1, 2 or 3 groups independently selected from methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, sec-butyl, fluoro, chloro, methyoxy, ethoxy, and trifluoromethyl.

4. The compound of claim 2 , wherein Z is a bond, —CH 2 —, —CH(CH 3 )—, or —CH 2 CH 2 —; and R 2 is H, halo, or C 1-4 alkyl optionally substituted with 1 to 3 halo.

5. The compound of claim 2 , wherein:

R 5 is a cyclobutyl, cyclopentyl, cyclohexyl, spiro[3.3]heptanyl, tricyclo[2.2.1.0 2,6 ]heptanyl, phenyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, bicyclo[2.2.2]octanyl, bicyclo[3.2.1]octanyl, bicyclo[3.3.1]nonanyl, bicyclo[3.2.2]nonanyl, 8-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl, 3-azabicyclo[3.1.0]hexanyl, azetidinyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,9-diazabicyclo[3.3.1]nonanyl, 4,7-diazaspiro[2.5]octanyl, benzofuran, benzo[d]oxazolyl, benzothiazolyl, benzothiophenyl, diazepinyl, morpholinyl, octahydro-1H-pyrido[1,2-a]pyrazinyl, octahydrocyclopenta[c]pyrrolyl, octahydropyrrolo[1,2-a]pyrazinyl, piperazinyl, piperidinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, and 5,6,7,8-tetrahydroimidazo[1,5-a]pyridinyl, wherein R 5 is substituted with 1, 2 or 3 groups selected from R 30 ;

R 30 in each occurrence is independently selected from 5- or 6-membered heteroaryl, C 1-4 alkyl, halo, CN, —S(O) 2 OR 30a , —C(O)N(R 30a )S(O) 2 R 30a , —C(O)N(R 30a )S(O) 2 R 30a , —P(O)(OR 30a ) 2 , —C(O) 2 R 30a , —OR 30a , and —C(O)R 30a , wherein said 5- or 6-membered heteroaryl and C 1-4 alkyl in each occurrence are optionally and independently substituted with 1, 2, or 3 R 35 , and the 5- or 6-membered heteroaryl is selected from pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyranyl, and pyrimidinyl, and

R 30a in each occurrence is independently selected from H and methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, sec-butyl;

R 35 in each occurrence is independently selected from halo, C 1-4 alkyl, and —C(O) 2 R 35a ; and

R 35a in each occurrence is independently selected from H and methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, sec-butyl.

6. The compound of claim 2 , wherein m is 1 and L is —NH—, —N(CH 3 )— or —O—; and R 4 is —C(O) 2 R 4a , —CN, —SO 3 R 4a , S(O) 2 R 4a , —CR 4a (CF 3 )OR 4a , or —C(CF 3 ) 2 OR 4a ; and R 4a in each occurrence is independently selected from H and C 1-4 alkyl.

7. The compound of claim 6 , wherein R 4 is —CO 2 H, —CO 2 —CH 3 , or —CO 2 —CH 2 CH 3 .

8. The compound of claim 1 , wherein the compound is represented by the following formula:

or a pharmaceutically acceptable salt thereof, wherein

Ring A is phenyl, optionally substituted with one or more halo;

R 5 is selected from 4- to 10-membered carbocyclyl and 4- to 10-membered heterocyclyl, wherein R 5 optionally substituted with one or more R 30 ;

R 30 in each occurrence is independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo and —C(O) 2 R 30a ; and

R 30a in each occurrence is independently selected from H and C 1-4 alkyl.

9. The compound of claim 8 , wherein

Ring A is phenyl, optionally substituted with one or two halo;

R 5 is selected from 9-azabicyclo[3.3.1]nonanyl, piperidinyl, and cyclohexyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, —CO 2 H, and —CF 3 .

10. The compound of claim 1 , wherein the compound is represented by the following formula:

or a pharmaceutically acceptable salt thereof, Ring A is phenyl, optionally substituted with one or more halo;

R 5 is selected from 4- to 10-membered carbocyclyl and 4- to 10-membered heterocyclyl, wherein R 5 optionally substituted with one or more R 30 ;

R 30 in each occurrence is independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo, and —C(O) 2 R 30a ; and

R 30a in each occurrence is independently selected from H and C 1-4 alkyl.

11. The compound of claim 10 , wherein

Ring A is phenyl, optionally substituted with one or two halo;

R 5 is cyclobutyl optionally substituted with 1, 2, or 3 groups independently selected from methyl or —CO 2 H.

12. The compound of claim 1 , wherein the compound is represented by the following formula:

or a pharmaceutically acceptable salt thereof, Ring A is phenyl, optionally substituted with one or more halo;

R 5 is selected from 4- to 10-membered carbocyclyl and 4- to 10-membered heterocyclyl, wherein R 5 optionally substituted with one or more R 30 ;

R 30 in each occurrence is independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo, and —C(O) 2 R 30a ; and

R 30a in each occurrence is independently selected from H and C 1-4 alkyl.

13. The compound of claim 12 , wherein

Ring A is phenyl, optionally substituted with one or two halo;

R 5 is selected from 9-azabicyclo[3.3.1]nonanyl, piperidinyl, pyrrolidinyl, tetrahydroimidazo[1,5-a]pyridinyl, bicyclo[2.2.2]octanyl, cyclobutyl, and cyclohexyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, —CO 2 H, —CO 2 CH 3 , —CH 2 CH 2 CO 2 H, and —CF 3 .

14. The compound of claim 1 , wherein the compound is represented by the following formula:

or a pharmaceutically acceptable salt thereof, Ring A is phenyl, optionally substituted with one or more halo;

R 5 is selected from 4- to 10-membered carbocyclyl and 4- to 10-membered heterocyclyl, wherein R 5 optionally substituted with one or more R 30 ;

R 30 in each occurrence is independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo and —C(O) 2 R 30a ; and

R 30a in each occurrence is independently selected from H and C 1-4 alkyl.

15. The compound of claim 14 , wherein

Ring A is phenyl, optionally substituted with one or two halo;

R 5 is selected from 9-azabicyclo[3.3.1]nonanyl, piperidinyl, bicyclo[2.2.2]octanyl, cyclobutyl, and cyclohexyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, —CO 2 H, —CO 2 CH 3 , and —CF 3 .

16. The compound of claim 1 , wherein the compound is represented by the following formula:

or a pharmaceutically acceptable salt thereof, Ring A is phenyl, optionally substituted with one or more halo;

R 5 is selected from 4- to 10-membered carbocyclyl and 4- to 10-membered heterocyclyl, wherein R 5 optionally substituted with one or more R 30 ;

R 30 in each occurrence is independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo, and —C(O) 2 R 30a ; and

R 30a in each occurrence is independently selected from H and C 1-4 alkyl.

17. The compound of claim 16 , wherein

Ring A is phenyl, optionally substituted with one or two halo;

R 5 is selected from 9-azabicyclo[3.3.1]nonanyl, piperidinyl, bicyclo[2.2.2]octanyl, cyclobutyl, and cyclohexyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, —CO 2 H, —CO 2 CH 3 , and —CF 3 .

18. A pharmaceutical composition comprising at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

19. The compound of claim 2 , wherein R 5 is cyclohexyl, cyclopentyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.2.1]octanyl, spiro[3.3]heptanyl, tricyclo[2.2.1.0 2,6 ]heptanyl, phenyl, piperidinyl, pyridinyl, pyrrolidinyl, azetidinyl, 8-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl, octahydrocyclopenta[c]pyrrolyl, 5,6,7,8-tetrahydroimidazo[1,5-a]pyridinyl, or benzothiazolyl, each of which is optionally substituted with 1 to 3 groups selected from —CO—CH 3 , —CO 2 H, —CH 2 —CO 2 H, —CH 2 —CH 2 —CO 2 H, —CO 2 —(C 1-4 alkyl), —CO 2 —(C 1-4 alkyl), C 1-4 alkyl optionally substituted with 1, 2, or 4 halo, halo, hydroxyl, and pyrimidinyl.

20. The compound of claim 1 , wherein the compound is selected from:

Ethyl 4-(2-(1 -(4-fluorobenzyl)-3 -(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-methylpiperidin-4-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-phenylethanone,

Ethyl 4-(2-(1-(4-chloro -2-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-cyclohexylethanone,

(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)(cyclohexyl)methanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(pyridin-4-yl)ethanone,

Ethyl 4-(2-(1-(4-chlorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

Ethyl 4-(2-(1-(2,4-dichlorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

Ethyl 4-(2-oxo-2-(3-(trifluoromethyl)-1-(4-(trifluoromethyl)benzyl)-4,5-dihydro -1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylate,

Methyl 4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)benzoate,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-fluorophenyl)ethanone,

Ethyl 4-(2-(1-benzyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

3-(Benzo[d]thiazol-2-yl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)propan-1-one,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-hydroxycyclohexyl)ethanone,

Ethyl 4-(2-(1-(cyclohexylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

Ethyl 4-(2-(1-(4-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

Ethyl 4-(2-(1-(3-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

Ethyl 4-(2-(1-(2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-7-yl)methanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-methylcyclohexyl)ethanone,

Methyl 4-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)cyclohexanecarboxylate,

Methyl 4-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)bicyclo[2.2.2]octane-1-carboxylate,

trans-Ethyl 4-(2-(1-cyclohexyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

trans-Ethyl 4-(2-(1-(4-methylbenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

trans-Ethyl 4-(2-(1-(4-methoxylbenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

Methyl 8-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)bicyclo[3.2.1]octane-3-carboxylate,

trans-Ethyl 4-(2-oxo-2-(1-phenethyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylate,

trans-Ethyl 4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

cis-Ethyl 4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

trans-Ethyl 4-(2-(1-(3-chloro-5-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

cis-ethyl 4-(2-(1-(3-chloro-5-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate,

cis-Methyl 4-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylate,

trans-Methyl 4-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylate,

cis-Methyl 4-(1-(4-chloro-2-fluorobenzyl)-N-methyl-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylate,

trans-Methyl 4-(1-(4-chloro-2-fluorobenzyl)-N-methyl-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylate,

4-(Ethoxycarbonyl)cyclohexyl1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine-6(7H)-carboxylate,

trans-4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-(3-chloro-5-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(3-chloro-5-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)benzoic acid,

cis-4-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylic acid,

trans-4-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylic acid,

4-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)bicyclo[2.2.2]octane-1-carboxylic acid,

cis-4-(1-(4-Chloro-2-fluorobenzyl)-N-methyl-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylic acid,

trans-4-(1-(4-Chloro-2-fluorobenzyl)-N-methyl-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carboxamido)cyclohexanecarboxylic acid,

4-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)bicyclo[2.2.2]octane-1-carboxylic acid,

4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)bicyclo[2.2.2]octane-1-carboxylic acid,

4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)bicyclo[2.2.2]octane-1-carboxylic acid,

trans-4-(2-(1-(4-Methylbenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-(4-Methoxylbenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-Oxo-2-(1-phenethyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-((5-chlorothiophen-2-yl)methyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

(2S)-1-(tert-Butoxycarbonyl)-4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylic acid,

trans-4-(2-(1-(1-(4-Fluorophenyl)ethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(1-(4-Fluorophenyl)ethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-Oxo-2-(1-phenyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid,

4-(2-(1-(3-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

4-(2-Oxo-2-(3-(trifluoromethyl)-1-(4-(trifluoromethyl)benzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid,

4-(2-(1-(2-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

4-(1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-1-oxopropan-2-yl)cyclohexanecarboxylic acid,

4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclohexanecarboxylic acid,

3-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclopentanecarboxylic acid,

3-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclopentanecarboxylic acid,

3-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclobutanecarboxylic acid,

3-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclobutanecarboxylic acid,

8-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)bicyclo[3.2.1]octane-3-carboxylic acid,

4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclohexanecarboxylic acid,

6-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)spiro[3.3]heptane-2-carboxylic acid,

6-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)spiro[3.3]heptane-2-carboxylic acid,

3-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-2,2-dimethylcyclobutanecarboxylic acid,

3-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-2,2-dimethylcyclobutanecarboxylic acid,

(3R,4R)-5-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)tricyclo[2.2.1.02,6]heptane-3-carboxylic acid,

(3R,4R)-5-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)tricyclo[2.2.1.02,6]heptane-3-carboxylic acid,

trans-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-(4-Chloro-2-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(4-chloro-2-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-(4-Chlorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(4-chlorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-(2,4-Dichlorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(2,4-dichlorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-((1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)oxy)cyclohexanecarboxylic acid,

trans-4-((1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)oxy)cyclohexanecarboxylic acid,

trans-4-(2-(1-Benzyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-benzyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4 4-(2-(1-(cyclohexylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4 4-(2-(1-(cyclohexylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-(4-Fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(4-Fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)cyclohexanecarboxylic acid,

cis-4-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-cyclohexyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-cyclohexyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

cis-4-(2-(1-(2-Cyclohexylethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

trans-4-(2-(1-(2-cyclohexylethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid,

tert-Butyl 3-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-8-azabicyclo[3.2.1]octane-8-carboxylate,

tert-Butyl 4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-1-carboxylate,

tert-Butyl 3-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azetidine-1-carboxylate,

tert-Butyl 3-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-1-carboxylate,

tert-Butyl 4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-2-methylpiperidine-1-carboxylate,

tert-Butyl 4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-2,2-dimethylpiperidine-1-carboxylate,

tert-Butyl 4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-2-(trifluoromethyl)piperidine-1-carboxylate,

2-(8-Aza-bicyclo[3.2.1]octan-3-yl)-1-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(piperidin-4-yl)ethanone,

2-(Azetidin-3-yl)- 1-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone,

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(piperidin-3-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(2-methylpiperidin-4-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(2,2-dimethylpiperidin-4-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(2-(trifluoromethyl)piperidin-4-yl)ethanone,

(2s)-4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylic acid,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(8-methyl-8-aza-bicyclo[3.2.1]octan-3-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1,2-dimethylpiperidin-4-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1,2,2-trimethylpiperidin-4-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-methyl-2-(trifluoromethyl)piperidin-4-yl)ethanone,

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-methylpiperidin-3-yl)ethanone formate,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-isopropylpiperidin-4-yl)ethanone,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-ethylpiperidin-4-yl)ethanone,

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-isopropylpiperidin-3-yl)ethanone formate,

Methyl 1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-4-carboxylate,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(piperidin-1-yl)ethanone,

Ethyl 1-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-3-carboxylate,

Methyl 8-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-8-azabicyclo[3.2.1]octane-3-carboxylate,

Ethyl 1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-3-carboxylate,

Ethyl 1-(1-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-1-oxopropan-2-yl)piperidine-4-carboxylate,

Methyl 1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidine-3-carboxylate,

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-(trifluoromethyl)piperidin-1-yl)ethanone,

Ethyl 3-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethylamino)propanoate,

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-4-carboxylic acid,

1-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-4-carboxylic acid,

1-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-3-carboxylic acid,

8-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-8-azabicyclo[3.2.1]octane-3-carboxylic acid,

8-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-8-azabicyclo[3.2.1]octane-3-carboxylic acid,

9-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-9-azabicyclo[3.3.1]nonane-3-carboxylic acid,

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-3-carboxylic acid,

1-(1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-1-oxopropan-2-yl)piperidine-4-carboxylic acid,

2-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)octahydrocyclopenta[c]pyrrole-5-carboxylic acid,

2-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)octahydrocyclopenta[c]pyrrole-5-carboxylic acid,

3-((2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)amino)-2,2-dimethylcyclobutanecarboxylic acid,

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidine-3-carboxylic acid,

2-(1-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidin-4-yl)acetic acid,

3-((2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)amino)-2,2-dimethylcyclobutanecarboxylic acid,

2-(1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidin-4-yl)acetic acid,

3-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethylamino)propanoic acid,

6-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-6-oxohexanoic acid,

5-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-5-oxopentanoic acid,

4-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-4-oxobutanoic acid,

2-(4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidin-1-yl)acetic acid,

3-(3-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)pyrrolidin-1-yl)propanoic acid,

3-(3-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)pyrrolidin-1-yl)propanoic acid,

Methyl 3-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)- 2-oxoethyl)piperidine-1-carboxylate,

Methyl 3-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-1-carboxylate, and

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-(pyrimidin-2-yl)piperidin-4-yl)ethanone,

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 1 , wherein the compound is selected from:

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(tetrahydro-2H-pyran-4-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(tetrahydro-2H-pyran-4-yl)ethanone;

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-3-(1H-tetrazol-5-yl)propan-1-one;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-3-(1H-tetrazol-5-yl)propan-1-one;

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(octahydroindolizin-7-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(octahydroindolizin-7-yl)ethanone;

(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)(quinuclidin-3-yl)methanone;

(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)(quinuclidin-4-yl)methanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(quinuclidin-3-yl)ethanone;

trans-Ethyl 4-(2-(3-(difluoromethyl)-1-(4-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate;

trans-Ethyl 4-(2-(3-cyclopropyl-1-(4-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate;

Ethyl 6-(2-(trans-4-(ethoxycarbonyl)cyclohexyl)acetyl)-1-(4-fluorobenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate;

trans-Ethyl-4-(2-(1-(4-fluorobenzyl)-3-(hydroxymethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate;

trans-Ethyl-4-(2-oxo-2-(1-(thiophen-3-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylate;

trans-Ethyl-4-(2-oxo-2-(1-(thiophen-2-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylate;

trans-Ethyl 4-(2-oxo-2-(1-(thiazol-5-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylate;

trans-Ethyl 4-(2-(1-((4-methylcyclohexyl)methyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate;

trans-Ethyl 4-(2-(1-(2,4-difluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylate;

trans-4-(2-Oxo-2-(1-(pyridin-3-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid;

trans-4-(2-Oxo-2-(1-(pyridin-2-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid;

trans-4-(2-Oxo-2-(1-(pyridin-4-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid;

cis-4-(2-(1-((5-Chlorothiophen-2-yl)methyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-Oxo-2-(1-(thiophen-2-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid;

trans-4-(2-Oxo-2-(1-(thiophen-3-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid;

trans-4-(2-Oxo-2-(1-(thiazol-5-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid;

trans-4-(2-Oxo-2-(1-(pyrimidin-5-ylmethyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethyl)cyclohexanecarboxylic acid;

trans-4-(2-(1-(2,4-Difluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-(1-(3,4-Difluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-(1-(2,4,5-Trifluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-(1-(3,4,5-Trifluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

cis-4-(2-(1-(2,4-Difluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

cis-4-(2-(1-(4-Cyanobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-(1-((4-Methylcyclohexyl)methyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-(3-Cyclopropyl-1-(4-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-(3-(Difluoromethyl)-1-(4-fluorobenzyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

trans-4-(2-(1-(4-Fluorobenzyl)-3-(hydroxymethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxylic acid;

2-(trans-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexyl)acetic acid;

2-(cis-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexyl)acetic acid;

4-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid;

4-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid;

4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)bicyclo[2.2.1]heptane-1-carboxylic acid;

4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)bicyclo[2.2.1]heptane-1-carboxylic acid;

4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)adamantancarboxylic acid;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(2-azaspiro[3.3]heptan-6-yl)adamantane carboxylic acid;

(2R)-1-(tert-Butoxycarbonyl)-4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylic acid;

3-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclobutanecarboxylic acid;

cis-3-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclobutanecarboxylic acid;

trans-3-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclobutanecarboxylic acid;

cis-4-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclohexanecarboxylic acid;

trans-4-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclohexanecarboxylic acid;

trans-4-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylcyclohexanecarboxylic acid;

tert-Butyl 2-ethyl-4-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-1-carboxylate;

tert-Butyl 4-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-2-propylpiperidine-1-carboxylate;

tert-Butyl 4-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)bicyclo[2.2.2]octan-1-ylcarbamate;

(4-Aminobicyclo[2.2.2]octan-1-yl)(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)methanone;

2-(4-Aminobicyclo[2.2.2]octan-1-yl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

2-(2-Ethylpiperidin-4-yl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(2-propylpiperidin-4-yl)ethanone acid;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(2-(trifluoromethyl)piperidin-4-yl)ethanone;

(2R)-4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylic acid;

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(morpholin-2-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(morpholin-2-yl)ethanone;

2-(cis-4-Aminocyclohexyl)-1-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

2-(cis-4-Aminocyclohexyl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

2-(trans-4-aminocyclohexyl)-1-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

2-(trans-4-Aminocyclohexyl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(octahydrocyclopenta[c]pyrrol-5-yl)ethanone;

(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)(4-(methylamino)bicyclo[2.2.2]octan-1-yl)methanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(pyrrolidin-3-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-methylpyrrolidin-3-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-isopropylpyrrolidin-3-yl)ethanone;

2-(2-Ethyl-1-methylpiperidin-4-yl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-methyl-2-propylpiperidin-4-yl)ethanone acid;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-methyl-2-propylpiperidin-4-yl)ethanone acid;

(2R)-4-(2-(1-(4-chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylpyrrolidine-2-carboxylic acid;

(2S)-4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-methylpyrrolidine-2-carboxylic acid;

(2S)-4-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-1-isopropylpyrrolidine-2-carboxylic acid;

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-4-carbonitrile;

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidine-3-carbonitrile;

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azetidine-3-carbonitrile;

1-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-methylpiperidin-1-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-methylpiperidin-1-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-(trifluoromethyl)piperidin-1-yl)ethanone;

Ethyl 1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azepane-4-carboxylate;

Ethyl 1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azepane-4-carboxylate;

Methyl 9-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-3-oxa-9-azabicyclo[3.3.1]nonane-7-carboxylate;

Methyl 2-(1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azetidin-3-yl)acetate;

1-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azetidine-3-carboxylic acid;

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azetidine-3-carboxylic acid;

1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azepane-4-carboxylic acid;

1-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azepane-4-carboxylic acid;

2-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-2-azaspiro[3.3]heptane-6-carboxylic acid;

2-(1-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azetidin-3-yl)acetic acid;

2-(1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)azetidin-3-yl)acetic acid;

2-(1-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidin-3-yl)acetic acid;

2-(1-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)pyrrolidin-3-yl)acetic acid;

9-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-3-oxa-9-azabicyclo[3.3.1]nonane-7-carboxylic acid;

9-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-3-oxa-9-azabicyclo[3.3.1]nonane-7-carboxylic acid;

cis-3-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethylamino)cyclobutanecarboxylic acid;

trans-3-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethylamino)cyclobutanecarboxylic acid;

cis-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethylamino)cyclohexanecarboxylic acid;

trans-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethylamino)cyclohexanecarboxylic acid;

3-(2-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethylamino)propanoic acid;

2-(3-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)pyrrolidin-1-yl)acetic acid;

2-(3-(1-(4-Chloro-2-fluorobenzyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-6-carbonyl)pyrrolidin-1-yl)acetic acid;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-(pyridin-2-yl)piperidin-4-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-(pyrimidin-4-yl)piperidin-4-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(1-(pyridin-4-yl)piperidin-4-yl)ethanone;

trans-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-N (methylsulfonyl)cyclohexane-carboxamide;

trans-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)-N-(methylsulfonyl)cyclohexanecarboxamide;

cis-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxamide;

trans-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarboxamide;

cis-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarbonitrile;

trans-4-(2-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)cyclohexanecarbonitrile;

2-(3-(Azetidin-1-yl)cyclobutyl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(octahydroindolizin-7-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(3-(pyrrolidin-1-yl)cyclobutyl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(3-(piperidin-1-yl)cyclobutyl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(3-morpholinocyclobutyl)ethanone;

2-(4-(Azetidin-1-yl)cyclohexyl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

2-(cis-4-(3,3-Difluoroazetidin-1-yl)cyclohexyl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

2-(trans-4-(3,3-difluoroazetidin-1-yl)cyclohexyl)-1-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone;

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-(pyrrolidin-1-yl)cyclohexyl)ethanone; and

1-(1-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-(4-morpholinocyclohexyl)ethanone;

or a pharmaceutically acceptable salt thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2017
From: KUMARAVEL, GNANASAMBANDAM; PENG, HAIRUO; XIN, ZHILI
To: BIOGEN MA INC.
Reel/Frame 041578/0431 →