IP Library Granted Patent US 9,394,282
Granted Patent B2
US 9,394,282 · App. 14/345,982 · Granted Jul 19, 2016

Pyrazole carboxamides as Janus kinase inhibitors

Inventors: Jason Brubaker (Cambridge, MA); Joshua Close (Franklin, MA); Tony Siu (Brookline, MA); Graham Frank Smith (Sudbury, MA); Luis E. Torres (Norwood, MA); Hyun Chong Woo (Natick, MA); Jonathan R. Young (Southborough, MA); Zhongyong Wei (Beijing, CN); Feng Shi (Beijing, CN)
Assignee: Merck Sharp & Dohme Corp.
C07D405/08C07D231/38C07D401/04C07D401/06C07D401/12C07D401/14C07D403/04C07D403/06C07D403/08C07D403/12C07D405/04C07D405/06C07D405/12C07D405/14C07D409/04C07D409/12C07D413/12C07D413/14C07D417/14
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Quick Facts
Patent No.
US 9,394,282
App. No.
14/345,982
Granted
Jul 19, 2016
Kind
B2
Abstract

The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.

Claims (778)

1. A compound of formula I or a pharmaceutically acceptable salt or stereoisomer thereof:

R a and R 4 are each independently chosen from hydrogen and C 1-4 alkyl;

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

p is 2, 3, or 4;

X is independently chosen from C, N, S, and O, wherein at least one X is other than carbon;

A is chosen from aryl, and heteroaryl;

R 2 and R 3 are each independently selected from:

hydrogen,

halogen,

C 1-10 alkyl,

C 2-10 alkenyl,

C 1-10 heteroalkyl,

aryl C 0-10 alkylC 0-10 alkyl,

C 3-8 cycloalkylC 0-10 alkyl,

heteroaryl C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl,

wherein each of R 2 and R 3 are independently substituted with 0, 1, 2, 3, or 4, substituents R 5a ;

R 5a is selected from:

hydrogen,

halogen,

C 1-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 heteroalkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 2-10 alkenyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 2-10 alkynyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 2-10 alkenyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 2-10 alkynyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

C 1-10 heteroalkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

C 2-10 alkenyl(carbonyl) 0-1 oxyC 0-10 alkyl,

C 1-10 heteroalkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

aryl C 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

(C 3-8 )cycloalkyl C 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

heteroarylC 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

((C 0-10 )alkyl) 1-2 aminocarbonyloxy,

(C 0-10 )heteroalkylaminocarbonyloxy,

aryl (C 0-10 )alkylaminocarbonyloxy,

(C 3-8 )cycloalkyl(C 0-10 )alkylaminocarbonyloxy,

heteroaryl(C 0-10 )alkylaminocarbonyloxy,

(C 3-8 )heterocycloalkyl(C 0-10 )alkylaminocarbonyloxy,

C 1-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

(C 0-10 )heteroalkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

aryl C 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

heteroarylC 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

(C 3-8 )heterocycloalkylC 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

C 1-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

C 1-10 heteroalkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

—CO 2 (C 0-10 alkyl),

—(C 0-10 alkyl)CO 2 H,

Oxo (═O),

C 1-10 alkylsulfonyl,

C 1-10 heteroalkylsulfonyl,

(C 3-8 ) cycloalkylsulfonyl,

(C 3-8 ) cycloheteroalkylsulfonyl,

heteroarylsulfonyl,

arylsulfonyl,

aminosulfonyl,

—SO 2 N(C 1-6 alkyl) 1-2 ,

—SO 2 C 1-6 alkyl,

—SO 2 CF 3 ,

—SO 2 CF 2 H,

C 1-10 alkylsulfinyl,

amino,

(C 0-10 alkyl) 1-2 amino,

C 1-4 acylamino C 0-10 alkyl,

hydroxy,

C 0-10 alkylalkoxy,

cyano,

C 1-6 alkylcyano, and

C 1-6 haloalkyl;

wherein R 5a is each optionally substituted with 0, 1, 2, 3, or 4 substituents, R 6 , independently selected from:

halogen,

C 1-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 heteroalkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 2-10 alkenyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 2-10 alkenyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 2-10 alkynyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

C 2-10 alkenyl(carbonyl) 0-1 oxyC 0-10 alkyl,

C 1-10 heteroalkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

aryl C 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

(C 3-8 )cycloalkyl C 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

heteroarylC 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

((C 0-10 )alkyl) 1-2 aminocarbonyloxy,

aryl (C 0-10 )alkylaminocarbonyloxy,

(C 3-8 )cycloalkyl(C 0-10 )alkylaminocarbonyloxy,

heteroaryl(C 0-10 )alkylaminocarbonyloxy,

(C 3-8 )heterocycloalkyl(C 0-10 )alkylaminocarbonyloxy,

C 1-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

aryl C 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

heteroaryl C 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

C 1-10 alkyl (oxy) 0-1 carbonylaminoC 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl (oxy) 0-1 carbonylaminoC 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

—CO 2 (C 0-10 alkyl),

—(C 0-10 alkyl)CO 2 H,

Oxo (═O),

C 1-10 alkylsulfonyl,

C 1-10 heteroalkylsulfonyl,

(C 3-8 ) cycloalkylsulfonyl,

(C 3-8 ) cycloheteroalkylsulfonyl,

heteroarylsulfonyl,

arylsulfonyl,

aminosulfonyl,

—SO 2 N(C 1-6 alkyl) 1-2 ,

—SO 2 C 1-6 alkyl,

—SO 2 CF 3 ,

—SO 2 CF 2 H,

C 1-10 alkylsulfinyl,

—OSi (C 6 H 15 )

amino,

(C 0-10 alkyl) 1-2 amino,

-(oxy) 0-1 (carbonyl) 0-1 N(C 0-10 alkyl) 1-2

C 1-4 acylamino C 0-10 alkyl,

hydroxy,

C 1-10 alkoxy,

cyano, and

C 1-6 haloalkyl; and

R 6 is optionally substituted with 0, 1, 2, or 3 substituents independently chosen from hydroxy, (C 1-6 )alkoxy, halogen, CO 2 H, —(C 0-6 )alkylCN, —O(C═O)C 1 -C 6 alkyl, NO 2 , trifluoromethoxy, trifluoroethoxy, —N—C(O)O(C 0-6 )alkyl, C 1-10 alkylsulfonyl, C 1-10 heteroalkylsulfonyl, oxo (O═), (C 3-8 ) cycloalkylsulfonyl, (C 3-8 ) cycloheteroalkylsulfonyl, heteroarylsulfonyl, arylsulfonyl, aminosulfonyl, —SO 2 N(C 1-6 alkyl) 1-2 , —SO 2 C 1-6 alkyl, —SO 2 CF 3 , —SO 2 CF 2 H, —C 1-10 alkylsulfinyl, —O—Si, —OSi(C 6 H 15 ), —O (0-1) (C 1-10 )haloalkyl, and NH 2 .

2. A compound according to claim 1 , wherein R a and R 4 are each hydrogen.

3. A compound according to claim 2 , wherein R 5a is independently selected from:

hydrogen,

halogen,

C 1-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 heteroalkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 2-10 alkynyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 2-10 alkenyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 2-10 alkenyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 2-10 alkynyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 alkyl(carbonyl) 0-1 oxyC 0-10 alkyl,

((C 0-10 )alkyl) 1-2 aminocarbonyloxy,

C 1-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

C 1-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

—CO 2 (C 0-10 alkyl),

—(C 0-10 alkyl)CO 2 H,

Oxo (═O),

C 0-10 alkylsulfonyl,

C 1-10 heteroalkylsulfonyl,

C 3-8 cycloalkylsulfonyl,

C 3-8 cyclohetroalkylsulfonyl,

heteroarylsulfonyl,

arylsulfonyl,

aminosulfonyl,

—SO 2 N(C 1-6 alkyl) 1-2 ,

—SO 2 C 1-6 alkyl,

—SO 2 CF 3 ,

—SO 2 CF 2 H,

C 1-10 alkylsulfinyl,

amino,

(C 0-10 alkyl) 1-2 amino,

hydroxy,

C 0-10 alkylalkoxy,

cyano,

C 1-6 alkylcyano, and

C 1-6 haloalkyl;

wherein R 5a is each optionally substituted with 0, 1, 2, 3, or 4 substituent, R 6 .

4. A compound according to claim 3 , wherein R 2 and R 3 are selected from hydrogen, C 1-10 alkyl, (C 3-8 )heterocycloalkyl C 0-10 alkyl, and C 3-8 cycloalkylC 0-10 alkyl, wherein each of R 2 and R 3 are independently substituted with 0, 1, 2, 3, or 4, substituents R 5a .

5. A compound according to claim 4 , wherein A is chosen from: furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, isoquinolinyl, naphthyridinyl, benzothienyl, benzofuranyl, benzimidazole, benzpyrazolyl, indolyl, isoindolyl, indolizinyl, indazolyl, purinyl, quinolizinyl, phthalazinyl, quinoxalinyl, quinazolinyl, benzoxazolyl, benzisoxazolyl, 5,6,7,8-tetrahydroquinolinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyrimidinyl, 5,6-dihydropyrrolo[1,2-b]pyrazolyl, pyrrolo[3,2-c]pyridinyl, pyrrolo[2,3-b]pyridinyl, thieno[2,3-b]pyrrolyl, furopyridine, thienopyridine, benzotriazolyl, indolyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromanyl, isochromanyl, tetrahydroquinolinyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzo-1,4-dioxinyl, imidazo(2,1-b)(1,3)thiazole, and benzo-1,3-dioxolyl, phenyl, indenyl, and naphthalenyl, wherein A is substituted with 0, 1, 2, 3, or 4, substituents, R 5a .

6. A compound according to claim 1 , wherein A is chosen from: phenyl, 1,3-dihydro-2H-isoindole, pyridinyl, quinolinyl, isoquinolinyl, 2,3-dihydro-1-benzofuranyl, dihydro-1H-indenyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3,dihydro-1H-isoindolyl, and benzo[b]thiophene, wherein A is substituted with 0, 1, 2, 3, or 4, substituents, R 5a .

7. A compound according to claim 6 , wherein R 2 and R 3 are independently selected from hydrogen, methyl, ethyl, propyl, tert-butyl, isopropyl, dimethylpropyl, dimethylbutyl, and tert-butylmethyl, and cyclobutyl.

8. A compound according to claim 7 , wherein R 5a is independently selected from: hydrogen, butynyloxycarbonyl, tert-butyloxycarbonyl, 3,3dimethylbutyloxycarbonyl, methylethyloxycarbonyl, Ethyloxycarbonyl, phenylpropyloxycarbonyl, morpholinylethyloxycarbonyl, oxetanyloxycarbonyl, methylpropyloxycarbonyl, piperidinylmethyloxycarbonyl, cyclopropylmethyloxycarbonyl, cyclopentyloxycarbonyl, benzyloxycarbonyl, tetrahydro-2H-pyranyloxycarbonyl, cyclopropylethyloxycarbonyl, pyrrolidinylethyloxycarbonyl, cyclohexyloxycarbonyl, dimethylpropyloxycarbonyl, propyloxycarbonyl, piprazininylethyloxycarbonyl, tetrahydrofuranyloxycarbonyl, piperidinyloxycarbonyl, pyrazolylethyloxycarbonyl, methyloxycarbonyl, oxetanylmethyloxycarbonyl, phenylethyloxycarbonyl, 2,3-dihydro-1H-indenyloxycarbonyl, methyloxycarbonyl, methylpropyloxycarbonyl, pyrazinylmethyl, isoxazolylmethyl, 1,3-oxazolylmethyl, pyrazolylmethyl, 1,3-thiazolylmethyl, pyridinylmethyl, cyclobutylmethyl, tetrahydro-2H-pyranylethyl, imidazolylmethyl, 4,5-dihydroisoxazolylmethyl, tetrhydrofuranylmethyl, pyridazinylmethyl, 4,5-dihydroisoxazolylmethyl, Oxo, methyl, halogen, trifluoromethyl, sulfonyl, (trifluoromethyl)sulfonyl, methoxy, hydroxyethyl, rifluroethyl, methylethyl, (difluoromethyl)ethyl, tetrahydro-2-H-pyranyl, difluoromethyl, dimethylaminocarbonyl, cyano, and ethoxy, wherein R 5a is independently substituted with 0, 1, 2, 3, or 4, substituents R 6 .

9. A compound according to claim 8 , wherein R 6 is independently selected from: methyl, fluoro, trifluoromethyl, cyano, amino, dimethylamino, oxo, hydroxyl, methoxy, cyclopropyl, ethyoxycarbonyl, cyano, fluoromethyl, methyethylhydroxy, ethyl, and difluoromethyl, wherein R 6 is optionally substituted with 1, 2, or 3 substituents chosen from hydrogen, hydroxy, (C 1-6 )alkoxy, halogen, CO 2 H, —(C 0-6 )alkylCN, —O(C═O)C 1 -C 6 alkyl, NO 2 , trifluoromethoxy, trifluoroethoxy, —N—C(O)O(C 0-6 )alkyl, C 1-10 alkylsulfonyl, C 1-10 heteroalkylsulfonyl, oxo (O═), (C 3-8 ) cycloalkylsulfonyl, (C 3-8 ) cycloheteroalkylsulfonyl, heteroarylsulfonyl, arylsulfonyl, aminosulfonyl, —SO 2 N(C 1-6 alkyl) 1-2 , —SO 2 C 1-6 alkyl, —SO 2 CF 3 , —SO 2 CF 2 H, —C 1-10 alkylsulfinyl, —O—Si, —OSi(C 6 H 15 ), —O (0-1) (C 1-10 )haloalkyl, and NH 2 .

10. A compound selected from:

tert-Butyl-4-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-3-cyanopiperidine-1-carboxylate,

tert-Butyl (3R,4S)-4-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-3-cyanopiperidine-1-carboxylate,

tert-Butyl (3S,4R)-4-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-3-cyanopiperidine-1-carboxylate,

tert-butyl (3S,4S)-4-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-3-cyanopiperidine-1-carboxylate,

tert-butyl (3R,4R)-4-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-3-cyanopiperidine-1-carboxylate,

tert-butyl-3-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-4-cyanopiperidine-1-carboxylate,

tert-butyl (3R,4S)-3-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-4-cyanopiperidine-1-carboxylate,

tert-butyl (3S,4R)-3-[4-(aminocarbonyl)-3-anilino-1H-pyrazol-1-yl]-4-cyanopiperidine-1-carboxylate,

tert-butyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

tert-butyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

tert-butyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

tert-butyl 4-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-3-cyanopiperidine-1-carboxylate,

(3R,4S)-tert-butyl 4-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-3-cyanopiperidine-1-carboxylate,

(3S,4R)-tert-butyl 4-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-3-cyanopiperidine-1-carboxylate,

1-[4-cyanopiperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanopiperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanopiperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[3-cyanopiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyanopiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4S)-3-cyanopiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

3,3-Dimethylbutyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

3,3-Dimethylbutyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

3,3-Dimethylbutyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-Trifluoro-1-methylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-Trifluoro-1-methylethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-Trifluoro-1-methylethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoroethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoroethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoroethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-phenylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-phenylpropyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-phenylpropyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-morpholin-4-ylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-morpholin-4-ylethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-morpholin-4-ylethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

oxetan-3-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

oxetan-3-yl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

oxetan-3-yl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyano-2-methylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyano-2-methylpropyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyano-2-methylpropyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylpiperidin-4-yl)methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylpiperidin-4-yl)methyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylpiperidin-4-yl)methyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-aminocyclopropyl)methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-aminocyclopropyl)methyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-aminocyclopropyl)methyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methylpropyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methylpropyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopentyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopentyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopentyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

benzyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

benzyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

benzyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(2-oxopyrrolidin-1-yl)ethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(2-oxopyrrolidin-1-yl)ethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(2-oxopyrrolidin-1-yl)ethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoroethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoroethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoroethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclohexyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclohexyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclohexyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-pyrrolidin-1-ylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-pyrrolidin-1-ylethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-pyrrolidin-1-ylethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-(dimethylamino)-2,2-dimethylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate;

3-(dimethylamino)-2,2-dimethylpropyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-(dimethylamino)-2,2-dimethylpropyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(dimethylamino)ethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(dimethylamino)ethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(dimethylamino)ethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

ethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

ethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate, ethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(4-methylpiperazin-1-yl)ethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(4-methylpiperazin-1-yl)ethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-(4-methylpiperazin-1-yl)ethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydrofuran-3-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydrofuran-3-yl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydrofuran-3-yl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-methylpiperidin-4-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-methylpiperidin-4-yl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-methylpiperidin-4-yl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methoxyethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methoxyethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methoxyethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopropylmethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopropylmethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopropylmethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate

2-fluoro-1-(fluoromethyl)ethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-methoxypropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-methoxypropyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-methoxypropyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

but-3-yn-1-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

but-3-yn-1-yl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

but-3-yn-1-yl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-phenylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-phenylethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-phenylethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,3-dihydro-1H-inden-2-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,3-dihydro-1H-inden-2-yl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,3-dihydro-1H-inden-2-yl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

but-3-yn-1-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

but-3-yn-1-yl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

but-3-yn-1-yl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,3-dihydro-1H-inden-2-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,3-dihydro-1H-inden-2-yl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,3-dihydro-1H-inden-2-yl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

ethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-3-cyanopiperidine-1-carboxylate,

ethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

ethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopropylmethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopropylmethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopropylmethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-phenylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-phenylethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-phenylethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopentyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopentyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclopentyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydrofuran-3-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydrofuran-3-yl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydrofuran-3-yl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

benzyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

benzyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

benzyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methoxyethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methoxyethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methoxyethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-phenylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-phenylpropyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-phenylpropyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methylpropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methylpropyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-methylpropyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

oxetan-3-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

oxetan-3-yl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

oxetan-3-yl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoroethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoroethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-fluoroethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclohexyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclohexyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

cyclohexyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-methoxypropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-methoxypropyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

3-methoxypropyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoroethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoroethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoroethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl (3R,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl (3S,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2-Cyano-2-methylpropyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-Cyano-2-methylpropyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-Cyano-2-methylpropyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-fluoro-1-(fluoromethyl)ethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

(1-methylcyclopropyl)methyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

1-cyclopropylethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

3-(dimethylamino)-2,2-dimethylpropyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

3-(dimethylamino)-2,2-dimethylpropyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

3-(dimethylamino)-2,2-dimethylpropyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

ethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-4-cyanopiperidine-1-carboxylate,

ethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

ethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methylpropyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methylpropyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methylpropyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-trifluoroethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-fluoroethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-fluoroethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-fluoroethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-dimethylpropyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

cyclopropylmethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

cyclopropylmethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

cyclopropylmethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

benzyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

benzyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

benzyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methoxyethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methoxyethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methoxyethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-4-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-ethoxy-2-oxoethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

tetrahydro-2H-pyran-4-yl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-(dimethylamino)ethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-(dimethylamino)ethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-(dimethylamino)ethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-morpholin-4-ylethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-yl}-4-cyanopiperidine-1-carboxylate,

2-morpholin-4-ylethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-morpholin-4-ylethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

[1-(cyanomethyl)cyclopropyl]methyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

oxetan-3-yl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

oxetan-3-yl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

oxetan-3-yl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

(3-methyloxetan-3-yl)methyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-cyclopropylethyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2-methyl-2-(1H-pyrazol-1-yl)propyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3S,4R)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2-difluoro-3-hydroxypropyl (3R,4S)-3-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl (3R,4R)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

2,2,2-trifluoro-1-methylethyl (3S,4S)-4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-3-cyanopiperidine-1-carboxylate,

1-[4-cyano-1-(pyridazin-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(pyridazin-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(pyridazin-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(pyrazin-2-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(pyrazin-2-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(pyrazin-2-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(isoxazol-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(isoxazol-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(isoxazol-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(1,3-oxazol-4-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(1,3-oxazol-4-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(1,3-oxazol-4-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(1-methyl-1H-pyrazol-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(1-methyl-1H-pyrazol-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(1-methyl-1H-pyrazol-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(1,3-thiazol-4-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(1,3-thiazol-4-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(1,3-thiazol-4-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(4-fluoropyridin-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(4-fluoropyridin-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(4-fluoropyridin-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(1,3-oxazol-2-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(1,3-oxazol-2-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(1,3-oxazol-2-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(3-methoxycyclobutyl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(3-methoxycyclobutyl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(3-methoxycyclobutyl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-{[3-(1-hydroxy-1-methylethyl)cyclobutyl]methyl}piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-{[3-(1-hydroxy-1-methylethyl)cyclobutyl]methyl}piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-{[3-(1-hydroxy-1-methylethyl)cyclobutyl]methyl}piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(cyclobutylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(cyclobutylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(cyclobutylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(4-cyano-1-[(1-methyl-1H-pyrazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(1-methyl-1H-pyrazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(1-methyl-1H-pyrazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(4-cyano-1-[(5-methylisoxazol-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(5-methylisoxazol-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(5-methylisoxazol-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(5-fluoropyridin-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(5-fluoropyridin-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(5-fluoropyridin-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(2-fluoropyridin-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(2-fluoropyridin-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(2-fluoropyridin-3-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(2-methyl-1,3-thiazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(2-methyl-1,3-thiazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(2-methyl-1,3-thiazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(1-ethyl-1H-imidazol-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(1-ethyl-1H-imidazol-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(1-ethyl-1H-imidazol-2-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(3-methyl-4,5-dihydroisoxazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(3-methyl-4,5-dihydroisoxazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4S)-4-cyano-1-[(3-methyl-4,5-dihydroisoxazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(tetrahydrofuran-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(tetrahydrofuran-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(tetrahydrofuran-3-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[3-cyano-1-(pyridazin-3-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyano-1-(pyridazin-3-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4S)-3-cyano-1-(pyridazin-3-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[3-cyano-1-(pyrazin-2-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyano-1-(pyrazin-2-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4S)-3-cyano-1-(pyrazin-2-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3-cyano-1-(isoxazol-3-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyano-1-(isoxazol-3-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4S)-3-cyano-1-(isoxazol-3-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[3-cyano-1-(1,3-oxazol-4-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyano-1-(1,3-oxazol-4-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4S)-3-cyano-1-(1,3-oxazol-4-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(1-methyl-1H-pyrazol-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(1-methyl-1H-pyrazol-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(1-methyl-1H-pyrazol-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[3-cyano-1-(1,3-thiazol-4-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyano-1-(1,3-thiazol-4-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4S)-3-cyano-1-(1,3-thiazol-4-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(5-fluoropyridin-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(5-fluoropyridin-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(5-fluoropyridin-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[3-cyano-1-(1,3-oxazol-2-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyano-1-(1,3-oxazol-2-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4S)-3-cyano-1-(1,3-oxazol-2-ylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(3-methoxycyclobutyl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(3-methoxycyclobutyl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(3-methoxycyclobutyl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(1-methyl-1H-pyrazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(1-methyl-1H-pyrazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(1-methyl-1H-pyrazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(5-methylisoxazol-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(5-methylisoxazol-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(5-methylisoxazol-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(2-fluoropyridin-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(2-fluoropyridin-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(2-fluoropyridin-3-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(6-fluoropyridin-2-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(6-fluoropyridin-2-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(6-fluoropyridin-2-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(2-methyl-1,3-thiazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(2-methyl-1,3-thiazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(2-methyl-1,3-thiazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(1-ethyl-1H-imidazol-2-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(1-ethyl-1H-imidazol-2-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(1-ethyl-1H-imidazol-2-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{3-cyano-1-[(3-methyl-4,5-dihydroisoxazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3R,4R)-3-cyano-1-[(3-methyl-4,5-dihydroisoxazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4S)-3-cyano-1-[(3-methyl-4,5-dihydroisoxazol-5-yl)methyl]piperidin-4-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[3-cyano-1-(cyclobutylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-3-cyano-1-(cyclobutylmethyl)piperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyano-1-(1,3-thiazol-5-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyano-1-(1,3-thiazol-5-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyano-1-(1,3-thiazol-5-ylmethyl)piperidin-3-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{4-cyano-1-[(4-methyl-1,3-oxazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R)-4-cyano-1-[(4-methyl-1,3-oxazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-{(3S,4R,3R,4S)-4-cyano-1-[(4-methyl-1,3-oxazol-5-yl)methyl]piperidin-3-yl}-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-(3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-(3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-(3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-(3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-((trifluoromethyl)sulfonyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-((trifluoromethyl)sulfonyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-((trifluoromethyl)sulfonyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R)-4-cyano-1,1-dioxidotetrahydrothiophen-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S)-4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R)-4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyano-tetrahydro-2H-pyran-3-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-(4-cyanotetrahydro-2H-pyran-3-yl)-3-((4-(trifluoromethoxy)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl)-3-((4-(trifluoromethoxy)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl)-3-((4-(trifluoromethoxy)phenyl)amino)-1H-pyrazole-4-carboxamide,

3-[(4-chlorophenyl)amino]-1-[4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-chlorophenyl)amino]-1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-chlorophenyl)amino]-1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R or 1S)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R or 1S)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R or 1S)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(4-cyanotetrahydro-2H-pyran-3-yl]-3-[(3,4-dichlorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(3,4-dichlorophenyl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(3,4-dichlorophenyl)amino]-1H-pyrazole-4-carboxamide,

3-[(4-chloro-3-fluorophenyl)amino]-1-[(4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-chloro-3-fluorophenyl)amino]-1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-chloro-3-fluorophenyl)amino]-1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1S)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1S)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(trifluoromethoxy)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(trifluoromethoxy)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(trifluoromethoxy)phenyl]amino}-1H-pyrazole-4-carboxamide,

3-[(7-chloroquinolin-3-yl)amino]-1-[4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(7-chloroquinolin-3-yl)amino]-1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(7-chloroquinolin-3-yl)amino]-1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(trifluoromethoxy)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(trifluoromethoxy)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(trifluoromethoxy)phenyl]amino}-1H-pyrazole-4-carboxamide,

3-[(4-chloro-3-fluorophenyl)amino]-1-[4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-chloro-3-fluorophenyl)amino]-1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-chloro-3-fluorophenyl)amino]-1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

1-[(4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(1-methoxy-1-methylethyl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(3-methyloxetan-3-yl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(3-methyloxetan-3-yl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(1-methoxy-1-methylethyl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(3-methyloxetan-3-yl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(1-methoxy-1-methylethyl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(3-methyloxetan-3-yl)phenyl]amino}-1H-pyrazole-4-carboxamide,

3-[(6-chloropyridin-3-yl)amino]-1-[(4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(6-chloropyridin-3-yl)amino]-1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(6-chloropyridin-3-yl)amino]-1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

1-[(4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(4-cyanotetrahydro-2H-pyran-3-yl]-3-[(6-fluoropyridin-3-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(6-fluoropyridin-3-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(6-fluoropyridin-3-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(4-cyanotetrahydro-2H-pyran-3-yl]-3-[(5-fluoropyridin-3-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(5-fluoropyridin-3-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(5-fluoropyridin-3-yl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(difluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(difluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(difluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(dimethylcarbamoyl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(dimethylcarbamoyl)phenyl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[4-(dimethylcarbamoyl)phenyl]amino}-1H-pyrazole-4-carboxamide,

3-[(4-cyanophenyl)amino]-1-[4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-cyanophenyl)amino]-1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

3-[(4-cyanophenyl)amino]-1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H-pyrazole-4-carboxamide,

1-[4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1R)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3S,4R)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1S)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-[(3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl]-3-({4-[(1S)-2,2-difluoro-1-hydroxy-1-methylethyl]phenyl}amino)-1H-pyrazole-4-carboxamide,

1-(4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S,6R)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R,6R)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R,6S)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S,6S)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S,6R)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S,6S)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R,6R)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R,6S)-4-Cyano-6-methyltetrahydro-2H-pyran-3-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide,

1-(3-cyano-tetrahydro-2H-pyran-4-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3R,4R)-3-cyano-tetrahydro-2H-pyran-4-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-((3S,4S)-3-cyano-tetrahydro-2H-pyran-4-yl)-3-(2-fluoropyridin-4-ylamino)-1H-pyrazole-4-carboxamide,

1-(3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-3-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-((4-(trifluoromethyl)phenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4R)-4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4S)-4-cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-(4-Cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3R,4R)-4-Cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide,

1-((3S,4S)-4-Cyano-4-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide; or a pharmaceutically acceptable salt or stereoisomer thereof.

11. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt, or a stereoisomer thereof and a pharmaceutically acceptable carrier.

12. A method for the treatment of a JAK-mediated disease comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or a stereoisomer, or a pharmaceutically acceptable thereof.

13. A method of treating a condition in a mammal that can be ameliorated by the selective inhibition of a Janus kinase JAK1 relative to JAK 2 and JAK 3 which condition is selected from arthritis, asthma, and obstructive airways diseases, autoimmune diseases or disorders, and cancer comprising administering to the mammal in need of such treatment, a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or a stereoisomer thereof.

14. A method according to claim 13 , wherein said condition is arthritis.

15. A method according to claim 14 , wherein said condition is selected from rheumatoid arthritis, juvenile arthritis, and psoriatic arthritis.

16. A method according to claim 13 , wherein said condition is asthma or obstructive airways diseases.

17. A method according to claim 13 , wherein said condition is selected from: chronic asthma, late asthma, airway hyper-responsiveness, bronchitis, bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma, dust asthma, recurrent airway obstruction, chronic obstruction pulmonary disease (COPD), and emphysema.

18. A method according to claim 13 , wherein said condition is autoimmune diseases or disorders.

19. A method of treating asthma in a mammal in need thereof, comprising administering a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or a stereoisomer, thereof.

20. A method of treating arthritis in a mammal in need thereof, comprising administering a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or stereoisomer, thereof.

Assignments (7)
CHANGE OF ADDRESS Recorded Sep 26, 2023
From: INTERVET INC.
To: INTERVET INC.
Reel/Frame 065028/0818 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 25, 2022
From: MERCK SHARP & DOHME CORP.
To: INTERVET INC.
Reel/Frame 059692/0765 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 9, 2014
From: WEI, ZHONGYONG; SHI, FENG
To: PHARMARON BEIJING CO., LTD.
Reel/Frame 032631/0782 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNORS PREVIOUSLY RECORDED ON REEL 032583 FRAME 0064. ASSIGNOR(S) HEREBY CONFIRMS THE NAMES OF ASSIGNORS ZHONGYONG WEI AND FENG SHI WERE ERRONEOUSLY RECORDED AND SHOULD BE REMOVED. Recorded Apr 9, 2014
From: BRUBAKER, JASON; CLOSE, JOSHUA; SIU, TONY; SMITH, GRAHAM FRANK; TORRES, LUIS E; WOO, HYUN CHONG; YOUNG, JONATHAN R
To: MERCK SHARP & DOHME CORP.
Reel/Frame 032641/0104 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2014
From: PHARMARON BEIJING CO., LTD.
To: PHARMARON, INC.
Reel/Frame 032583/0228 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2014
From: BRUBAKER, JASON; CLOSE, JOSHUA; SIU, TONY; SMITH, GRAHAM FRANK; TORRES, LUIS E; WOO, HYUN CHONG; YOUNG, JONATHAN R; WEI, ZHONGYONG; SHI, FENG
To: MERCK SHARP & DOHME CORP.
Reel/Frame 032583/0064 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2014
From: PHARMARON, INC.
To: MERCK SHARP & DOHME CORP.
Reel/Frame 032583/0171 →
Continuity (2)
Provisional Application 61537978 · Sep 22, 2011
Related Publication 20140235641A1 · Aug 21, 2014