US2023128198A1PendingUtilityA1
Novel heterocyclic compounds useful as aurora a selective inhibitors
Assignee: JACOBIO PHARMACEUTICALS CO LTDPriority: Jan 22, 2020Filed: Jan 22, 2021Published: Apr 27, 2023
Est. expiryJan 22, 2040(~13.5 yrs left)· nominal 20-yr term from priority
C07D 413/14C07D 401/14C07D 417/14A61K 45/06C07D 405/14C07D 409/14A61P 35/00C07D 401/12A61P 35/04A61K 31/506A61K 31/4545C07D 407/14A61K 31/496A61K 2300/00A61K 31/5377C07D 451/02C07D 417/12C07D 471/08
58
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Claims
Abstract
Provided are compounds of formula (I), or pharmaceutically acceptable salts thereof, which can be used for inhibiting the activity of Aurora A and treating cancer mediated by Aurora A.
Claims
exact text as granted — not AI-modified1 - 166 . (canceled)
167 . A compound of Formula VI or Formula VII, or a pharmaceutically acceptable salt thereof:
Y 1 is selected from CH or CR Y1 ;
Y 2 is selected from CH or CR Y2 ;
wherein R Y1 and R Y2 is independently selected from deuterium, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —NO 2 , —NH(C 1-3 alkyl), —N(C 1-3 alkyl) 2 , —COOH, —CONH 2 , —CO—C 1-3 alkyl, —S—C 1-3 alkyl, —SO—C 1-3 alkyl, —SO 2 , —SO 2 C 1-3 alkyl, C 1-3 lkyl, C 1-3 alkoxy, —CO—C 3-6 heterocyclic ring, 3-membered carbocyclic ring, 4-membered carbocyclic ring, 5-membered carbocyclic ring, 6-membered carbocyclic ring, 7-membered carbocyclic ring, 8-membered carbocyclic ring, 5-membered aryl, 6-membered aryl, 3-membered heterocyclic ring, 4-membered heterocyclic ring, 5-membered heterocyclic ring, 6-membered heterocyclic ring, 7-membered heterocyclic ring, 8-membered heterocyclic ring, 5-membered heteroaryl or 6-membered heteroaryl, and each of the heterocyclic ring and heteroaryl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of which is independently optionally substituted with deuterium, —F, —Cl, —Br, —I, —NH 2 , —CN, —OH, —NO 2 , carbonyl, ═O, oxo, carboxyl, C 1-3 alkoxy, C 1-3 alkyl, —NH(C 1-3 alkyl), —N(C 1-3 alkyl) 2 , —S—C 1-3 alkyl, or —SO 2 C 1-3 alkyl;
each X 1 and X 2 is independently selected from —H, deuterium, —CN, —OH, —NH 2 , C 1-3 alkyl, or C 1-3 alkoxy;
Y is selected from —(CH 2 ) m —CR 4 R 5 —(CH 2 ) m —;
m is independently 0;
R 4 and R 5 is independently selected from —H or deuterium;
Ar 2 is a 6-membered aryl, 5-membered heteroaryl or 9-membered heteroaryl, and each of the heteroaryl contains 1 or 2 heteroatoms selected from N, O or S; and each of which is independently optionally substituted with one or more of deuterium, —F, —Cl, —Br, —CN, —OH, —NH 2 , carbonyl, ═O, oxo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —CH 2 F, —CHF 2 , —CF 3 , —CH 2 D, CHD 2 , —CD 3 ; and
Ar 1 is 5-membered heteroaryl which contains 1, 2 or 3 heteroatoms selected from N or S, and which is independently optionally substituted with one or more of deuterium; —F; —Cl; —Br; —I; —CN; —OH; —NH 2 ; carbonyl; ═O; oxo; methyl; ethyl; propyl; isopropyl; methoxy; ethoxy; propoxy; isopropoxy; —CH 2 F, —CHF 2 , —CF 3 , —CH 2 D, CHD 2 , —CD 3 , —CH 2 NHmethyl, —CH 2 NHethyl, —CH 2 NHpropyl, —CH 2 NHisopropyl, —CH 2 N(CH 3 ) 2 .
168 . The compound or pharmaceutically acceptable salt thereof of claim 167 , wherein R Y1 and R Y2 is independently selected from deuterium, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —NO 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHmethyl, —NHethyl, —NHpropyl, —NHisopropyl, —N(CH 3 ) 2 , —COOH, —CONH 2 , —COCH 3 , —COCH 2 CH 3 , —CO—CH(CH 3 ) 2 , —SCH 3 , —SOCH 3 , —SO 2 , —SO 2 CH 3 , —CO-4-membered heterocyclic ring, —CO-5-membered heterocyclic ring, —CO-6-membered heterocyclic ring, 3-membered carbocyclic ring, 4-membered carbocyclic ring, 5-membered carbocyclic ring, 6-membered aryl, 3-membered heterocyclic ring, 4-membered heterocyclic ring, 5-membered heterocyclic ring, 6-membered heterocyclic ring, 5-membered heteroaryl or 6-membered heteroaryl, and each of the heterocyclic ring and heteroaryl independently optionally contains 1 or 2 heteroatoms selected from N, O or S; and each of which is independently optionally substituted with deuterium, —F, —Cl, —Br, —I, —NH 2 , —CN, —OH, —NO 2 , carbonyl, ═O, oxo, carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy;
each X 1 and X 2 is independently selected from —H, deuterium, —CN, —OH, —NH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, or isopropoxy;
Y is selected from —CH 2 —;
Ar 2 is a phenyl, and each of which is independently optionally substituted with one or more of deuterium, —F, —Cl, —Br, —CN, —OH, —NH 2 , carbonyl, ═O, oxo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —CH 2 F, —CHF 2 , —CF 3 , —CH 2 D, CHD 2 , —CD 3 ; or
Ar 1 is
and which is independently optionally substituted with one or more of deuterium, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , carbonyl, ═O, oxo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, or isopropoxy.
169 . The compound or pharmaceutically acceptable salt thereof of claim 167 , wherein R Y1 and R Y2 is independently selected from deuterium, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —NO 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHmethyl, —NHethyl, —NHpropyl, —NHisopropyl, —N(CH 3 ) 2 , —COOH, —CONH 2 , —COCH 3 , —COCH 2 CH 3 , —CO—CH(CH 3 ) 2 , —SCH 3 , —SOCH 3 , —SO 2 , —SO 2 CH 3 ,
and each of which is independently optionally substituted with deuterium, —F, —Cl, —NH 2 , —CN, —OH, carbonyl, ═O, oxo, carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy;
each X 1 and X 2 is independently —H, methyl, or ethyl;
Ar 2 is
Ar 1 is
170 . The compound or pharmaceutically acceptable salt thereof of claim 167 , wherein R Y1 and R Y2 is independently selected from deuterium, —F, —Cl, —CN, —OH, methyl, ethyl, isopropyl, —NHmethyl, —COOH, —COCH 3 , —COCH 2 CH 3 , —CO—CH(CH 3 ) 2 , —CO—C(CH 3 ) 3 , —COCF 3 , —SOCH 3 , —SO 2 , —SO 2 CH 3 , —CHF 2 , —CF 3 , —CH(F)CH 3 , —C(F) 2 CH 3 , —OCH 3 , —OCF 3 , —CH 2 OH, —CH 2 CH 2 OH, —CHOHCH 3 , —CH 2 F, —CH 2 D, CHD 2 , —CD 3 , —CH 2 CH 2 F, —CH 2 CHF 2 , —CH 2 CD 3 , —CH 2 CF 3 , —CH 2 CH 2 NH 2 , —CH 2 CH 2 NHCH 3 , —CH 2 CH 2 N(CH 3 ) 2 , —CH 2 CH 2 CH 2 F, —CH 2 CH 2 CD 3 , —CH 2 CH 2 CF 3 , —CH 2 N(CH 3 ) 2 , —CH(CH 3 )(CD 3 ), —CH(CF 3 ) 2 , —CH(CD 3 ) 2 , —CH 2 NHmethyl, —CH 2 NHethyl, —CH 2 NHpropyl,
171 . The compound or pharmaceutically acceptable salt thereof of claim 167 , wherein the compound is of Formula VII:
wherein,
Y 1 is independently CH or CR Y1 ;
Y 2 is independently CH or CR Y2 ;
R Y1 and R Y2 is independently selected from deuterium, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —CO—C 1-3 alkyl, C 1-3 lkyl, or C 1-3 alkoxy; and each of which is independently optionally substituted with deuterium or —F;
Y is selected from —CH 2 —;
each X 1 and X 2 is independently selected from —H, deuterium, —F, —Cl, —CN, —OH, —NH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, or isopropoxy;
Ar 2 is a 6-membered aryl, and which is optionally substituted with one or more of deuterium, —F, —Cl, methyl, ethyl, propyl, isopropyl, —CH 2 D, CHD 2 or —CD 3 ;
Ar 1 is 5-membered heteroaryl which contains 1 or 2 heteroatoms selected from N or S, and which is independently optionally substituted with one or more of deuterium; —F; —Cl; —CN; methyl; ethyl; propyl; isopropyl; —CH 2 D, CHD 2 , —CD 3 .
172 . The compound or pharmaceutically acceptable salt thereof of claim 171 , R Y1 and R Y2 is independently selected from deuterium, —F, —Cl, —Br, —I, —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —COCH 3 , —COCH 2 CH 3 , —CO—C(CH 3 ) 2 ; and each of which is independently optionally substituted with deuterium, or —F;
each X 1 and X 2 is independently selected from —H or methyl;
Ar 2 is a phenyl, and which is optionally substituted with one or more of deuterium, —F, —Cl, methyl, ethyl, propyl, —CH 2 D, CHD 2 or —CD 3 ;
Ar 1 is
and which is independently optionally substituted with one or more of deuterium, —F, —CN, methyl, or ethyl.
173 . The compound or pharmaceutically acceptable salt thereof of claim 171 , R Y1 and R Y2 is independently selected from deuterium, —F, —Cl, —CN, methyl, ethyl, isopropyl, —COCH 3 , —CHF 2 , —CF 3 , —COCH 3 , —COCH 2 CH 3 , —CO—C(CH 3 ) 2 , —CH(F) CH 3 , —C(F) 2 CH 3 , —CH 2 F, —CH 2 D, CHD 2 , —CD 3 , —CH 2 CH 2 F, —CH 2 CHF 2 , —CH 2 CD 3 , —CH 2 CH 2 CD 3 , —CH(CD 3 ) 2 ,
Ar 2 is
Ar 1 is
174 . The compound or pharmaceutically acceptable salt thereof of claim 167 , wherein the compound is
1.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)piperidine-4-carboxylic acid
2.
1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
3.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-2,6-dimethylpiperidine-4-carboxylic acid
4.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-(thiazol-2-ylamino)pyridin-2-yl)methyl)-2-
methylpiperidine-4-carboxylic acid
5.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((5-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
6.
(2R,4R)-1-(3-chloro-2,6-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
8.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
9.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyclopropyl-3-fluoro-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
12.
(2R,4R)-1-(2,6-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
13.
(2R,4R)-1-(2,6-dimethylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
14.
(2R,4R)-1-(2,3-dichlorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
15.
(2R,4R)-1-(2,3-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
16.
(2R,4R)-1-(2-fluoro-3-methylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
17.
(2R,4R)-1-(2,6-dichlorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
18.
(2R,4R)-1-(3-chloro-4-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
19.
(2R,4R)-1-(4-chloro-3-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
20.
(2R,4R)-1-(3,5-dichlorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
21.
(2R,4R)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methyl-
1-(3-(trifluoromethyl)benzyl)piperidine-4-carboxylic acid
22.
(2R,4R)-1-(3,4-dichloro-5-fluorobenzyl)-4-((3 -fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
23.
(2R,4R)-1-(3,5-dichloro-4-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
24.
(2R,4R)-1-(3,5-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
27.
(2R,4R)-1-(3-chloro-2,4-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
34.
(2R,4R)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methyl-
1-(2-(trifluoromethyl)benzyl)piperidine-4-carboxylic acid
35.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-5-methyl-6-((3-methyl-1H-pyrazol-5-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
44.
(2R,4R)-1-(2-(3-chloro-2-fluorophenyl)-2-oxoethyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
46.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-(oxetan-
3-yl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
47.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(3-hydroxyoxetan-3-yl)-6-((5-methyl-
1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
48.
(2R,4R)-1-(3 -chloro-2-fluorobenzyl)-4-((3-fluoro-4-(3fluorooxetan-3-yl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
49.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
50.
(2R,4R)-1-(3-chloro-2,6-difluorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
51.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
52.
1-(2,3-difluorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
53.
(2R,4R)-1-(2,3-dichlorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
54.
1-(2,3-dichlorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
55.
1-(3-chloro-2,6-difluorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
61.
(2R,4R)-1-(2,3-difluorobenzyl)-4-((3-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
62.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(2-hydroxypropan-2-yl)-6-((5-methyl-
1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
63.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-isopropyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
64.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-(difluoromethyl)-3-fluoro-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
65.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-ethyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
66.
1-(3-chloro-2-fluorobenzyl)-4-((4-ethyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
67.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyano-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
68.
(2R,4R)-4-((4-acetyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-
(3-chloro-2-fluorobenzyl)-2-methylpiperidine-4-carboxylic acid
69.
4-((4-acetyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-(3-chloro-
2-fluorobenzyl)piperidine-4-carboxylic acid
70.
(2R,4R)-4-((4-acetyl-5-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-
1-(3-chloro-2-fluorobenzyl)-2-methylpiperidine-4-carboxylic acid
71.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-(1,1-difluoroethyl)-3-fluoro-6-((5-methyl-IH-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
72.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-chloro-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
73.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-chloro-5-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
74.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-chloro-3,5-difluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
75.
(2R,4R)-4-((4-(azetidin-1-yl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-1-(3-chloro-2-fluorobenzyl)-2-methylpiperidine-4-carboxylic acid
76.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(1-hydroxyethyl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
77.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(1-fluoroethyl)-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
78.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((5-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
79.
1-(3-chloro-2-fluorobenzyl)-4-((5-fluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
80.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
propionylpyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
81.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(methylsulfonyl)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
82.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((5-fluoro-3,4-dimethyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
83.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3′-fluoro-6′-((5-methyl-1H-pyrazol-3-yl)amino)-[2,4′-
bipyridin]-2′-yl)methyl)-2-methylpiperidine-4-carboxylic acid
85.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-isobutyryl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
90.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyano-5-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
91.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3,5-difluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
92.
1-(3-chloro-2-fluorobenzyl)-4-((3,5-difluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
93.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3,5-difluoro-4-methyl-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
94.
(2R,4R)-4-((6-((1H-pyrazol-3-yl)amino)-3-fluoro-4-(2-fluoropropan-2-yl)pyridin-2-
yl)methyl)-1-(3-chloro-2-fluorobenzyl)-2-methylpiperidine-4-carboxylic acid
96.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((4-fluoro-5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
97.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-2-(trifluoromethyl)piperidine-4-carboxylic acid
100.
(2R,4R)-1-(2-chloro-6-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
101.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-cyano-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
102.
1-(3-chloro-2-fluorobenzyl)-4-((6-((4,5-dimethyl-1H-pyrazol-3-yl)amino)-3-fluoropyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
103.
1-(3-chloro-2-fluorobenzyl)-4-((6-((4-cyano-5-methyl-1H-pyrazol-3-yl)amino)-3-fluoropyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
104.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyano-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
106.
1 -(3 -chloro-2-fluorobenzyl)-4-((3-fluoro-4-(3-hydroxy oxetan-3-yl)-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
107.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(3-hydroxyazetidin-1-yl)-6-((5-methylthiazol-2-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
108.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-(4-
methylpiperazin-1-yl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
122.
(2R,4R)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-
(2-(trifluoromethyl)benzyl)piperidine-4-carboxylic acid
130.
(2R,6R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2,6-dimethylpiperidine-4-carboxylic acid
131.
(3R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-3-methylpiperidine-4-carboxylic acid
132.
(2R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
133.
(2R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
134.
1-(3-chloro-2,6-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
135.
(2R)-1-(3-chloro-2,6-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
136.
(2R)-1-(3-chloro-2,6-difluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
137.
1-(3-chloro-2,4-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
138.
(2R)-1-(3-chloro-2,4-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
139.
(2R)-1-(3-chloro-2,4-difluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
140.
1-(2,3-dichlorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)piperidine-4-carboxylic acid
141.
(2R)-1-(2,3-dichlorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-2-methylpiperidine-4-carboxylic acid
142.
(2R)-1-(2,3-dichlorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
143.
1-(2,3-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)piperidine-4-carboxylic acid
144.
(2R)-1-(2,3-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-2-methylpiperidine-4-carboxylic acid
145.
(2R)-1-(2,3-difluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
146.
1-(3-chloro-2-fluoro-6-methylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
147.
(2R)-1-(3-chloro-2-fluoro-6-methylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
148.
(2R)-1-(3-chloro-2-fluoro-6-methylbenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
149.
1-(3-chloro-2-methylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)piperidine-4-carboxylic acid
150.
(2R)-1-(3-chloro-2-methylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
151.
(2R)-1-(3-chloro-2-methylbenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
152.
4-((6-((1H-pyrazol-3-yl)amino)-3-fluoropyridin-2-yl)methyl)-1-(2-fluoro-3-
methylbenzyl)piperidine-4-carboxylic acid
153.
(2R)-4-((6-((1H-pyrazol-3-yl)amino)-3-fluoropyridin-2-yl)methyl)-1-(2-fluoro-3-
methylbenzyl)-2-methylpiperidine-4-carboxylic acid
154.
(2R)-4-((6-((1H-pyrazol-3-yl)amino)-3-fluoropyridin-2-yl)methyl)-2-ethyl-1-(2-fluoro-3-
methylbenzyl)piperidine-4-carboxylic acid
155.
4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-(2-
fluorobenzyl)piperidine-4-carboxylic acid
156.
(2R)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-(2-
fluorobenzyl)-2-methylpiperidine-4-carboxylic acid
157.
(2R)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-(2-
fluorobenzyl)piperidine-4-carboxylic acid
158.
1-(2,6-dichlorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)piperidine-4-carboxylic acid
159.
(2R)-1-(2,6-dichlorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-2-methylpiperidine-4-carboxylic acid
160.
(2R)-1-(2,6-dichlorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
161.
1-(2,6-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)piperidine-4-carboxylic acid
162.
(2R)-1-(2,6-difluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-2-methylpiperidine-4-carboxylic acid
163.
(2R)-1-(2,6-difluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
164.
1-(3-chloro-2-fluoro-4-methylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
165.
(2R)-1-(3-chloro-2-fluoro-4-methylbenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
166.
(2R)-1-(3-chloro-2-fluoro-4-methylbenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
178.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
179.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-4-(3-hydroxyoxetan-3-yl)-6-((5-
methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
180.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(oxetan-3-yl)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
181.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)-4-(oxetan-3-yl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
182.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(3-hydroxyazetidin-1-yl)-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
183.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-4-(3-hydroxyazetidin-1-yl)-6-((5-
methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
184.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(3-hydroxyazetidin-1-yl)-6-((5-methyl-
1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
185.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(4-methylpiperazin-1-yl)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
186.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)-4-(4-methylpiperazin-1-yl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
187.
(2R,4R)-4-((4-(azetidin-3-yl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-
yl)methyl)-1-(3-chloro-2-fluorobenzyl)-2-methylpiperidine-4-carboxylic acid
188.
4-((4-(azetidin-3-yl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-
(3-chloro-2-fluorobenzyl)piperidine-4-carboxylic acid
189.
(2R,4R)-4-((4-(azetidin-3-yl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)
methyl)-1-(3-chloro-2-fluorobenzyl)-2-ethylpiperidine-4-carboxylic acid
190.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(l-methylazetidin-3-yl)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
191.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-(1-
methylazetidin-3-yl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
192.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)-4-(l-methylazetidin-3-yl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
193.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-4-methyl-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
194.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((4-ethyl-3-fluoro-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
195.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-isopropyl-6-((5-methyl-1H-pyrazol-3-yl)amino)
pyridin-2-yl)methyl)piperidine-4-carboxylic acid
196.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-4-isopropyl-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
197.
1-(3-chloro-2-fluorobenzyl)-4-((4-cyclopropyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
198.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyclopropyl-3-fluoro-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)-2-ethylpiperidine-4-carboxylic acid
199.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(2-hydroxypropan-2-yl)-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
200.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-4-(2-hydroxypropan-2-yl)-6-((5-
methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
201.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
phenylpyridin-2-yl)methyl)piperidine-4-carboxylic acid
202.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
phenylpyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
203.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)-4-phenylpyridin-2-yl)methyl)piperidine-4-carboxylic acid
204.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(l-hydroxycyclopropyl)-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
205.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(l-hydroxycyclopropyl)-6-((5-methyl-
1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
206.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-4-(l-hydroxycyclopropyl)-6-((5-
methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
207.
(2R,4R)-4-((4-(azetidin-1-yl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)
methyl)-1-(3-chloro-2-fluorobenzyl)-2-ethylpiperidine-4-carboxylic acid
208.
4-((4-(azetidin-1-yl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-
(3-chloro-2-fluorobenzyl)piperidine-4-carboxylic acid
209.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-(difluoromethyl)-3-fluoro-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-ethylpiperidine-4-carboxylic acid
210.
1-(3-chloro-2-fluorobenzyl)-4-((4-(difluoromethyl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
211.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)-4-(trifluoromethyl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
212.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(trifluoromethyl)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
213.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(trifluoromethyl)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
214.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-2-ethyl-4-((3-fluoro-4-(l-hydroxycyclobutyl)-6-((5-
methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
215.
1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(l-hydroxycyclobutyl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
216.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(l-hydroxycyclobutyl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
217.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyclobutyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-ethylpiperidine-4-carboxylic acid
218.
1-(3-chloro-2-fluorobenzyl)-4-((4-cyclobutyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)
pyridin-2-yl)methyl)piperidine-4-carboxylic acid
219.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyclobutyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
220.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((4-cyano-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)-2-ethylpiperidine-4-carboxylic acid
221.
1-(3-chloro-2-fluorobenzyl)-4-((4-cyano-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-
2-yl)methyl)piperidine-4-carboxylic acid
324.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(methylamino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
325.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-isopropoxy-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
326.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(l-fluorocyclopropyl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
327.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(2-hydroxyethyl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
336.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-(2-fluoro-1,3-dihydroxypropan-2-yl)-6-
((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic
acid
338.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
morpholinopyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
342.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(3-methyloxetan-3-yl)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
346.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)-4-
(trifluoromethoxy)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
348.
1-(3-chloro-2,6-difluorobenzyl)-4-((4-ethyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)
pyridin-2-yl)methyl)piperidine-4-carboxylic acid
349.
4-((4-acetyl-3-fluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-1-(3-chloro-
2,6-difluorobenzyl)piperidine-4-carboxylic acid
465.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3,5-difluoro-4-((R)-1-fluoroethyl)-6-((5-methyl-
1H-pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
480.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3,5-difluoro-4-isobutyryl-6-((5-methyl-1H-pyrazol-
3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
482.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-((R)-1-fluoroethyl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
483.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3-fluoro-4-((S)-1-fluoroethyl)-6-((5-methyl-1H-
pyrazol-3-yl)amino)pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid
491.
1-(3-chloro-2-fluorobenzyl)-4-((4-(1,1-difluoroethyl)-3-fluoro-6-((5-methyl-1H-pyrazol-3-
yl)amino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid
492.
(2R,4R)-1-(3-chloro-2-fluorobenzyl)-4-((3,4-difluoro-6-((5-methyl-1H-pyrazol-3-yl)amino)
pyridin-2-yl)methyl)-2-methylpiperidine-4-carboxylic acid.
175 . A pharmaceutical composition comprising a therapeutically effective amount of at least one compound or pharmaceutically acceptable salt thereof of claim 167 and at least one pharmaceutically acceptable excipient.
176 . The pharmaceutical composition of claim 175 , wherein, the said compound or pharmaceutically acceptable salt thereof in a weight ratio to the said excipient within the range from about 0.0001 to about 10.
177 . The pharmaceutical composition of claim 175 , further comprising at least one of additional active ingredient.
178 . A method of treating a patient, comprising administering to the patient a therapeutically effective amount of at least one compound or pharmaceutically acceptable salt thereof as defined in claim 167 .
179 . A method for the treatment or prevention of cancer or cancer metastasis, comprising administering to the patient a therapeutically effective amount of at least one compound or pharmaceutically acceptable salt thereof as defined in claim 167 .
180 . The method of claim 179 , wherein the cancer is selected from the group consisting of small cell lung cancer, colorectal cancer, gastric cancer, prostate cancer, breast cancer, triple-negative breast cancer, cervical cancer, head and neck cancer, esophageal cancer, ovarian cancer, non-small cell lung cancer, non-Hodgkin lymphoma, or any of combination thereof.
181 . The method of claim 179 , wherein the cancer is selected from small cell lung cancer, prostate cancer, triple-negative breast cancer, cervical cancer, or head and neck cancer.
182 . A method of treating a patient having a condition which is mediated by the activity of Aurora A, said method comprising administering to the patient a therapeutically effective amount of at least one compound or pharmaceutically acceptable salt thereof as defined in claim 167 .
183 . The method of claim 182 , wherein the condition mediated by the activity of Aurora A is cancer.
184 . The method of claim 182 , wherein the condition mediated by the activity of Aurora A is small cell lung cancer, colorectal cancer, gastric cancer, prostate cancer, breast cancer, triple-negative breast cancer, cervical cancer, head and neck cancer, esophageal cancer, ovarian cancer, non-small cell lung cancer, non-Hodgkin lymphoma, or any of combination thereof.
185 . The method of claim 183 , wherein the cancer is selected from small cell lung cancer, prostate cancer, triple-negative breast cancer, cervical cancer, or head and neck cancer.
186 . A method of treating cancer selected from the group consisting of small cell lung cancer, colorectal cancer, gastric cancer, prostate cancer, breast cancer, triple-negative breast cancer, cervical cancer, head and neck cancer, esophageal cancer, ovarian cancer, non-small cell lung cancer, or non-Hodgkin lymphoma in a mammal comprising administering to a mammal in need of such treatment an effective amount of at least one compound or pharmaceutically acceptable salt thereof as defined in claim 167 .Join the waitlist — get patent alerts
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