US 11,999,699 B2Granted

Substituted pyrazole amides

AssigneeGrüNenthal GmbH

InventorsSebastian Krueger, Sebastian Peil, Clemens Dialer, Marcel Muelbaier, Markus Wagener, Ingo Konetzki, Nikolay Sitnikov, Jo Alen, Martin Pettersson

Life of this patent

Estimating the term…

Abstract

The present invention relates to compounds according to general formula (I) which act as inhibitors of NaV1.8 and can be used in the treatment of pain.

Claims16

Dependent claims

A compound according to general formula (I)

wherein
L represents CH2, CH(CH3) or CH(CH2CH3);
R1 represents C3-10-cycloalkyl, or 4 to 10-membered heterocycloalkyl,
R2 represents H or C1-6-alkyl;
X represents phenyl, or 5 to 10-membered heteroaryl;
R3 represents S(O)2—C1-6-alkyl, S(O)2—(C3-6-cycloalkyl), S(O)2-(4 to 6-membered heterocycloalkyl), S(O)2-phenyl, S(O)2-(5 or 6-membered heteroaryl), S(O)—NH2, S(O)—N(H)(C1-6-alkyl), S(O)—N(C1-6-alkyl)2, S(O)2—NH2, S(O)2—N(H)(C1-6-alkyl), S(O)2—N(H)(C3-6-cycloalkyl), S(O)2—N(C1-6-alkyl)2, C(O)—NH2, C(O)—N(H)(C1-6-alkyl), C(O)—N(H)(C3-6-cycloalkyl), C(O)—N(C1-6-alkyl)2, C(O)—N(C1-6-alkyl)(C3-6-cycloalkyl), OCF3, OCF2H, CN, OH, O—C3-6-cycloalkyl, O-(4 to 6-membered heterocycloalkyl), S(O)—C1-6-alkyl, S(O)—(C3-6-cycloalkyl), S(O)-(4 to 6-membered heterocycloalkyl), S(O)-phenyl, or S(O)-(5 or 6-membered heteroaryl);
R4 and R5 independently from one another represent H, F, Cl, Br, CN, CHF2, CH2F, CF3, C1-6-alkyl, C3-10-cycloalkyl, C1-6-alkylene-C3-10-cycloalkyl, 4 to 10-membered heterocycloalkyl, C1-6-alkylene-(4 to 10-membered heterocycloalkyl), NH2, N(H)(C1-6-alkyl), N(C1-6-alkyl)2, O—C1-6-alkyl, O—C3-10-cycloalkyl, O—C1-6-alkylene-C3-10-cycloalkyl, O-(4 to 6-membered heterocycloalkyl), or O—C1-6-alkylene-(4 to 6-membered heterocycloalkyl), provided that at least one of R4 and R5 does not represent H;
wherein C1-6-alkyl and C1-6-alkylene in each case independently from one another is linear or branched;
wherein C1-6-alkyl, C1-6-alkylene, C3-10-cycloalkyl, C3-6-cycloalkyl, 4 to 10-membered heterocycloalkyl and 4 to 6-membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with F;
and/or are unsubstituted or monosubstituted with one substituent selected from the group consisting of Cl, CN, C1-6-alkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, CF3, CF2H, CFH2, C(O)—C1-6-alkyl, OH, ═O, OCF3, OCF2H, OCFH2, O—C1-6-alkyl, C1-4-alkylene-O—C1-4-alkylene-O—CH3, and C0-4-alkylene-O—(C1-4-alkylene-O)1-4—CH3;
wherein phenyl, 5 to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from the group consisting of F, Cl, Br, CN, C1-6-alkyl, C3-6-cycloalkyl, CF3, CF2H, CFH2, C1-6-alkylene-CF3, C1-6-alkylene-CF2H, C1-6-alkylene-CFH2, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C(O)—C1-6-alkyl, OCF3, OCF2H, OCFH2, and O—C1-6-alkyl;
in the form of the free compound or a physiologically acceptable salt thereof.

9 more elements

A compound selected from the group consisting of:

SC-01
2-(cyclohexylmethyl)-N-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-3-
carboxamide
SC-02
2-[ (4,4-difluorocyclohexyl)methyl] -N-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-
3-carboxamide;
SC-03
2-(cyclopentylmethyl)-N-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-04
N-(3-methylsulfonylphenyl)-2-(oxan-4-ylmethyl)-5-(trifluoromethyl)pyrazole-3-carboxamide;
SC-05
2-[ (4,4-difluorocyclohexyl)methyl] -N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-
3-carboxamide;
SC-06
2-(cyclohexylmethyl)-4,5-dimethyl-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-07
1-(cyclohexylmethyl)-3,4-dimethyl-N-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazole-5-
carboxamide;
SC-08
2-(cyclohexylmethyl)-4-fluoro-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-09
1-(cyclohexylmethyl)-3-(difluoromethyl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazole-5-
carboxamide;
SC-10
4-cyano-2-(cyclohexylmethyl)-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-11
2-(cyclohexylmethyl)-5-methyl-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-12
2-(cyclohexylmethyl)-5-cyclopropyl-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-13
2-[ (4,4-difluorocyclohexyl)methyl] -N-(4-fluoro-3-methylsulfonylphenyl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-14
2-[ (4,4-difluorocyclohexyl)methyl] -N-(2-methylsulfonylpyridin-4-yl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-15
2-[ (4,4-difluorocyclohexyl)methyl] -N-(5-methylsulfonylpyridin-3-yl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-16
2-[ (4,4-difluorocyclohexyl)methyl] -N-(2-fluoro-3-methylsulfonylphenyl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-17
2-(cyclohexylmethyl)-5-methoxy-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-18
2-(cyclohexylmethyl)-N-(3-methylsulfonylphenyl)-4-propan-2-ylpyrazole-3-carboxamide;
SC-19
2-(cyclohexylmethyl)-4-cyclopropyl-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-21
N-(4-carbamoyl-3-fluorophenyl)-1-[ (4,4-difluorocyclohexyl)methyl] -4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-22
2-[ (4,4-difluorocyclohexyl)methyl] -N-(2-fluoro-5-methylsulfonylphenyl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-23
2-[ (3,3-difluorocyclohexyl)methyl] -N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-
3-carboxamide;
SC-24
2-(cyclobutylmethyl)-N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-3-carboxamide;
SC-25
2-(cyclopentylmethyl)-N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-26
2-(cyclohexylmethyl)-N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-27
2-(cycloheptylmethyl)-N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-28
N-(3-methylsulfonylphenyl)-2-(oxan-4-ylmethyl)-4-(trifluoromethyl)pyrazole-3-carboxamide;
SC-29
2-(1-cyclohexylethyl)-N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-30
1-(cyclohexylmethyl)-N-(2-oxo-l,2-dihydropyridin-4-yl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamide;
SC-31
2-(cycloheptylmethyl)-N-(2-hydroxypyridin-4-yl)-4-(trifluoromethyl)pyrazole-3-carboxamide;
SC-32
2-(1-cyclohexylethyl)-N-(2-hydroxypyridin-4-yl)-4-(trifluoromethyl)pyrazole-3-carboxamide;
SC-33
2-(cyclohexylmethyl)-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)pyrazole-3-carboxamide;
SC-35
N-(3-carbamoyl-4-fluorophenyl)-1-(cyclohexylmethyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamide;
SC-36
2-(cyclohexylmethyl)-N-(1-methylsulfonylpyrazol-4-yl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-37
2-(cyclohexylmethyl)-4-methyl-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-38
5-cyano-2-(cyclohexylmethyl)-N-(3-methylsulfonylphenyl)pyrazole-3-carboxamide;
SC-39
N-(3-carbamoyl-4-fluorophenyl)-2-[ (4,4-difluorocyclohexyl)methyl] -4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-41
N-(3-carbamoylphenyl)-2-[ (4,4-difluorocyclohexyl)methyl] -4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-42
2-[ (4,4-difluorocyclohexyl)methyl] -N-(3-fluoro-5-methylsulfonylphenyl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-43
2-[ (4,4-difluorocyclohexyl)methyl] -N-(3-sulfamoylphenyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-44
2-[ (4,4-difluorocyclohexyl)methyl] -4,5-dimethyl-N-(3-methylsulfonylphenyl)pyrazole-3-
carboxamide;
SC-45
3,4-dimethyl-N-(3-sulfamoylphenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-5-
carboxamide;
SC-46
2-(cyclohexylmethyl)-5-methyl-N-(3-methylsulfonylphenyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-47
N-(3-carbamoyl-4-fluorophenyl)-2-[ (4,4-difluorocyclohexyl)methyl] -5-methyl-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-48
2-[ (4,4-difluorocyclohexyl)methyl] -N-(4-fluoro-3-sulfamoylphenyl)-4,5-dimethylpyrazole-3-
carboxamide;
SC-49
2-[ (4,4-difluorocyclohexyl)methyl] -N-(4-fluoro-3-sulfamoylphenyl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-50
4-[ [ 2-[ (4,4-difluorocyclohexyl)methyl] -4-(trifluoromethyl)pyrazole-3-
carbonyl] amino] pyridine-2-carboxamide;
SC-51
2-[ (4,4-difluorocyclohexyl)methyl] -4,5-dimethyl-N-(3-sulfamoylphenyl)pyrazole-3-
carboxamide;
SC-52
N-(3-(methylsulfonyl)phenyl)-1-((tetrahydro-2H-pyran-3-yl)methyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-53
2-(cyclohexylmethyl)-N-(1-methylsulfonylpyrrolo[ 2,3-b] pyridin-3-yl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-54
5-methyl-N-(3-methylsulfonylphenyl)-2-(oxan-3-ylmethyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-55
5-methyl-N-(3-methylsulfonylphenyl)-2-(oxan-2-ylmethyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-56
5-methyl-N-(3-methylsulfonylphenyl)-2-(oxolan-2-ylmethyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-57
2-[ (4,4-difluorocyclohexyl)methyl] -5-methyl-N-(3-sulfamoylphenyl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-60
2-[ (3,3-difluorocyclopentyl)methyl] -N-(3-sulfamoylphenyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-61
N-(3-carbamoylphenyl)-2-[ (4,4-difluorocyclohexyl)methyl] -5-methyl-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-62
2-[ (4,4-difluorocyclohexyl)methyl] -5-methyl-N-(3-methylsulfonylphenyl)-4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-63
3-methyl-N-(3-(methylsulfonyl)phenyl)-1-((tetrahydrofuran-3-yl)methyl)-4-(trifluoromethyl)-
lH-pyrazole-5-carboxamide;
SC-64
2-(cyclohexylmethyl)-N-(2-hydroxypyridin-4-yl)-5-methyl-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-65
N-(3-carbamoyl-4-fluorophenyl)-2-[ (4,4-difluorocyclohexyl)methyl] -4,5-dimethylpyrazole-3-
carboxamide;
SC-66
N-(2-hydroxypyridin-4-yl)-5-methyl-2-(oxan-4-ylmethyl)-4-(trifluoromethyl)pyrazole-3-
carboxamide;
SC-67
N-(2-hydroxypyridin-4-yl)-3-methyl-1-((tetrahydro-2H-pyran-3-yl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-68
N-(2-hydroxypyridin-4-yl)-3-methyl-1-((tetrahydro-2H-pyran-2-yl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-69
2-[ (4,4-difluorocyclohexyl)methyl] -N-(2-sulfamoylpyridin-4-yl)-4-(trifluoromethyl)pyrazole-
3-carboxamide;
SC-73
N-(3-carbamoyl-4-fluorophenyl)-2-[ (3,3-difluorocyclopentyl)methyl] -4-
(trifluoromethyl)pyrazole-3-carboxamide;
SC-77
4-[ [ 2-[ (4,4-difluorocyclohexyl)methyl] -4,5-dimethylpyrazole-3-carbonyl] amino] pyridine-2-
carboxamide;
SC-78
(1-((3,3-difluorocyclopentyl)methyl)-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-80
1-((3,3-difluorocyclopentyl)methyl)-N-(2-sulfamoylpyridin-4-yl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-82
1-((3,3-difluorocyclopentyl)methyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-4-(trifluoromethyl)-
1H-pyrazole-5-carboxamide;
SC-84
4-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-85
1-((4,4-difluorocyclohexyl)methyl)-3-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-86
4-(1-((4,4-difluorocyclohexyl)methyl)-4-(difluoromethyl)-3-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-87
1-((4,4-difluorocyclohexyl)methyl)-4-(difluoromethyl)-3-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-88
N-(3-carbamoyl-4-fluorophenyl)-1-((4,4-difluorocyclohexyl)methyl)-4-(difluoromethyl)-3-
methyl-1H-pyrazole-5-carboxamide;
SC-89
1-((4,4-difluorocyclohexyl)methyl)-4-(difluoromethyl)-3-methyl-N-(3-sulfamoylphenyl)-1H-
pyrazole-5-carboxamide;
SC-90
4-(3-chloro-1-((4,4-difluorocyclohexyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-91
3-chloro-1-((4,4-difluorocyclohexyl)methyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-92
N-(3-carbamoyl-4-fluorophenyl)-3-chloro-1-((4,4-difluorocyclohexyl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-93
3-chloro-1-((4,4-difluorocyclohexyl)methyl)-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-94
4-(1-((4,4-difluorocyclohexyl)methyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-95
1-((4,4-difluorocyclohexyl)methyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-96
N-(3-carbamoyl-4-fluorophenyl)-1-((4,4-difluorocyclohexyl)methyl)-4-methyl-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-97
1-((4,4-difluorocyclohexyl)methyl)-4-methyl-N-(3-sulfamoylphenyl)-3-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-98
4-(1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-99
1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-100
N-(3-carbamoyl-4-fluorophenyl)-1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-4-
methyl-lH-pyrazole-5-carboxamide;
SC-101
1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-4-methyl-N-(3-sulfamoylphenyl)-1H-
pyrazole-5-carboxamide;
SC-102
4-(4-chloro-1-((4,4-difluorocyclohexyl)methyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-103
4-chloro-1-((4,4-difluorocyclohexyl)methyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-104
N-(3-carbamoyl-4-fluorophenyl)-4-chloro-1-((4,4-difluorocyclohexyl)methyl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-105
4-chloro-1-((4,4-difluorocyclohexyl)methyl)-N-(3-sulfamoylphenyl)-3-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-106
1-((3,3-difluorocyclopentyl)methyl)-3-methyl-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-108
1-((3,3-difluorocyclopentyl)methyl)-3-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-110
4-(1-((3,3-difluorocyclopentyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-112
N-(3-carbamoyl-4-fluorophenyl)-1-((3,3-difluorocyclopentyl)methyl)-3-methyl-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-114
1-((3,3-difluorocyclopentyl)methyl)-4-methyl-N-(3-sulfamoylphenyl)-3-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-116
1-((3,3-difluorocyclopentyl)methyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-118
4-(1-((3,3-difluorocyclopentyl)methyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-120
N-(3-carbamoyl-4-fluorophenyl)-1-((3,3-difluorocyclopentyl)methyl)-4-methyl-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-122
4-(3-methyl-1-((3,3,4,4-tetrafluorocyclopentyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-123
3-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((3,3,4,4-tetrafluorocyclopentyl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-124
4-(1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-125
1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-126
N-(3-carbamoyl-4-fluorophenyl)-1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-127
1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-N-(3-sulfamoylphenyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-128
4-(3-cyclopropyl-1-((4,4-difluorocyclohexyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-129
4-(3-cyclopropyl-1-((3,3-difluorocyclopentyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-131
4-(3-cyclopropyl-1-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-132
3-cyclopropyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-133
4-(3-cyclopropyl-1-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethoxy)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-134
4-(3-methoxy-1-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-135
4-(3-cyclopropyl-1-((2-methyltetraliydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-138
4-(3-cyclopropyl-1-((5-methyltetraliydrofuran-3-yl)methyl)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-139
4-(3-cyclopropyl-1-((5-methyltetrahydrofuran-2-yl)methyl)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-140
N-(3-carbamoyl-4-fluorophenyl)-3-cyclopropyl-1-((tetrahydro-2H-pyran-2-yl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-141
N-(3-carbamoyl-4-fluorophenyl)-1-((3,3-difluorocyclobutyl)methyl)-3-(difluoromethyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-143
4-(3-cyclopropyl-1-((6-methyltetrahydro-2H-pyran-2-yl)methyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-144
4-(3-cyclopropyl-1-((3,3-difluorocyclobutyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-145
4-(3-cyclopropyl-1-((tetraliydro-2H-pyran-3-yl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-147
4-(3-cyclopropyl-4-(trifluoromethyl)-1-((2-(trifluoromethyl)tetrahydrofuran-3-yl)methyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-148
4-(3-cyclopropyl-4-(trifluoromethyl)-1-((5-(trifluoromethyl)tetrahydrofuran-3-yl)methyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-149
4-(4-chloro-1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-150
3-cyclopropyl-N-(2-(methylsulfonyl)pyridin-4-yl)-4-(trifluoromethyl)-1-((2-
(trifluoromethyl)tetrahydrofuran-3-yl)methyl)-1H-pyrazole-5-carboxamide;
SC-151
3-cyclopropyl-1-((3,3-difluorocyclobutyl)methyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-153
3-cyclopropyl-4-(difluoromethyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((tetrahydro-2H-
pyran-4-yl)methyl)-1H-pyrazole-5-carboxamide;
SC-154
4-(3-cyclopropyl-1-((2,2-difluorocyclobutyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-155
4-(1-((3,3-difluorocyclopentyl)methyl)-3-isopropoxy-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-156
4-(1-((3,3-difluorocyclopentyl)methyl)-3-ethoxy-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-157
4-(3-(cyclopropylmethoxy)-1-((3,3-difluorocyclopentyl)methyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-158
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(difluoromethoxy)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-159
4-(1-(cyclobutylmethyl)-3-cyclopropyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-160
4-(4-chloro-1-((3,3-difluorocyclopentyl)methyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-161
4-(1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-163
4-(1-((4,4-difluorocyclohexyl)methyl)-3-(difluoromethyl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-165
1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-166
3-(1,1-difluoroethyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((3,3,4,4-
tetrafluorocyclopentyl)methyl)-1H-pyrazole-5-carboxamide;
SC-167
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-168
4-(3-(1,1-difluoroethyl)-4-methyl-1-((3,3,4,4-tetrafluorocyclopentyl)methyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-169
1-((3,3-difluorocyclobutyl)methyl)-3-isopropyl-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-170
4-(1-((3,3-difluorocyclobutyl)methyl)-3-isopropyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-171
1-((3,3-difluorocyclobutyl)methyl)-3-ethyl-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-172
4-(1-((3,3-difluorocyclobutyl)methyl)-3-ethyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-173
1-((3,3-difluorocyclobutyl)methyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-4-(trifluoromethyl)-3-
(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-5-carboxamide;
SC-174
4-(1-((3,3-difluorocyclobutyl)methyl)-4-(trifluoromethyl)-3-(1,1,1-trifluoropropan-2-yl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-175
1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoropropan-2-yl)-N-(2-(methylsulfonyl)pyridin-
4-yl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-176
4-(1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoropropan-2-yl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-177
4-(4-chloro-1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoroethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-178
4-chloro-1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-179
1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoroethyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-
4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-180
4-(1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-181
1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-
4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-182
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-183
1-((3,3-difluorocyclobutyl)methyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-3-
(perfluoroethyl)-1H-pyrazole-5-carboxamide;
SC-184
4-(1-((3,3-difluorocyclobutyl)methyl)-4-methyl-3-(perfluoroethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-185
1-((3,3-difluorocyclopentyl)methyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-3-
(perfluoroethyl)-1H-pyrazole-5-carboxamide;
SC-186
4-(1-((3,3-difluorocyclopentyl)methyl)-4-methyl-3-(perfluoroethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-187
1-((3,3-difluorocyclobutyl)methyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-3-(1,1,1-
trifluoropropan-2-yl)-1H-pyrazole-5-carboxamide;
SC-188
4-(1-((3,3-difluorocyclobutyl)methyl)-4-methyl-3-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-189
1-((3,3-difluorocyclopentyl)methyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-3-(1,1,1-
trifluoropropan-2-yl)-1H-pyrazole-5-carboxamide;
SC-190
4-(1-((3,3-difluorocyclopentyl)methyl)-4-methyl-3-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-191
1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoropropan-2-yl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-192
4-(1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoropropan-2-yl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-193
1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoropropan-2-yl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-194
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoropropan-2-yl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-195
1-((3,3-difluorocyclopentyl)methyl)-3-(difluoromethoxy)-N-(2-(methylsulfonyl)pyridin-4-yl)-
4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-196
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(difluoromethoxy)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-197
1-((3,3-difluorocyclopentyl)methyl)-3-(difluoromethoxy)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-198
4-(1-((3,3-difluorocyclopentyl)methyl)-4-methyl-3-(trifluoromethoxy)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-199
1-((3,3-difluorocyclopentyl)methyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-3-
(trifluoromethoxy)-1H-pyrazole-5-carboxamide;
SC-200
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethoxy)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-201
1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethoxy)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-202
3-(cyclopropyldifluoromethyl)-1-((3,3-difluorocyclobutyl)methyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-203
4-(3-(cyclopropyldifluoromethyl)-1-((3,3-difluorocyclobutyl)methyl)-4-methyl-1H-pyrazole-
5-carboxamido)picolinamide;
SC-204
4-(3-(1,1-difluoroethyl)-4-methyl-1-((2-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-205
3-(1,1-difluoroethyl)-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((2-
(trifluoromethyl)cyclopropyl)methyl)-1H-pyrazole-5-carboxamide;
SC-206
4-(3-(1,1-difluoroethyl)-1-((2-(difluoromethyl)cyclopropyl)methyl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-207
3-(1,1-difluoroethyl)-1-((2-(difluoromethyl)cyclopropyl)methyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-208
4-(1-((3,3-difluoro-1-methyleyclobutyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-1H-pyrazole-
5-carboxamido)picolinamide;
SC-209
1-((3,3-difluoro-1-methyleyclobutyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-
sulfamoylpyridin-4-yl)-1H-pyrazole-5-caiboxamide;
SC-210
1-((3,3-difluoro-1-methyleyclobutyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-211
1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-sulfamoylpyridin-4-
yl)-1H-pyrazole-5-ca±oxamide;
SC-212
1-((3,3-difluoro-1-methylcyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-
sulfamoylpyridin-4-yl)-1H-pyrazole-5-caiboxamide;
SC-213
1-((3,3-difluoro-1-methylcyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-214
4-(1-((3,3-difluoro-1-methyleyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-1H-pyrazole-
5-carboxamido)picolinamide;
SC-215
1-((3,3-difluorocyclobutyl)methyl)-3-(l,1-difluoroethyl)-4-methyl-N-(2-sulfamoylpyridin-4-
yl)-1H-pyrazole-5-ca±oxamide;
SC-216
4-(3-cyclopropyl-1-((3,3-difluorocyclopentyl)methyl)-4-(difluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-217
4-(1-((4,4-difluoro-2-(trifluoromethyl)cyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-
lH-pyrazole-5-carboxamido)picolinamide;
SC-218
4-(1-((3,3-difluorocyclopentyl)methyl)-3-ethyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-219
4-(3-cyclopropyl-1-((3-(trifluoromethoxy)cyclobutyl)methyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-220
1-((3,3-difluoro-1-(trifluoromethyl)cyclobutyl)methyl)-3-(l,l-difluoroethyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-221
4-(3-cyclopropyl-1-((3-(difluoromethyl)cyclobutyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-222
1-(1-(3,3-difluorocyclobutyl)ethyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-223
4-(3-(1,1-difluoroethyl)-1-((2-((2-methoxyethoxy)methyl)cyclohexyl)methyl)-4-methyl-1H-
pyrazole-5-carboxamido)picolinamide;
SC-224
1-((3,4-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-225
1-((3,3-difluorocyclopentyl)methyl)-3-methoxy-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-226
1-(cyclohexylmethyl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazole-5-carboxamide;
SC-229
1-(cyclohexylmethyl)-4-(difluoromethyl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazole-5-
carboxamide;
SC-230
3-cyclopropyl-1-((4,4-difluorocyclohexyl)methyl)-N-(3-sulfamoylphenyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-231
N-(2-cyanopyridin-4-yl)-1-((4,4-difluorocyclohexyl)methyl)-3,4-dimethyl-1H-pyrazole-5-
carboxamide;
SC-232
1-((1-methylcyclohexyl)methyl)-N-(3-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-233
1-((1-fluorocyclohexyl)methyl)-N-(3-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-234
3-methyl-N-(3-(methylsulfonyl)phenyl)-1-(oxetan-3-yimethyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-235
1-((2,2-difluorocyclopentyl)methyl)-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamide;
SC-236
4-chloro-1-((4,4-difluorocyclohexyl)methyl)-3-methyl-N-(3-sulfamoylphenyl)-1H-pyrazole-
5-carboxamide;
SC-237
3-methyl-N-(3-(methylsulfonyl)phenyl)-1-(oxetan-2-ylmethyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-238
1-(cyclohexylmethyl)-N-(4-fluoro-3-sulfamoyiphenyl)-3-methyl-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-239
4-(3-chloro-1-((4,4-difluorocyclohexyl)methyl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-241
1-((4,4-difluorocyclohexyl)methyl)-3-methyl-N-(5-(methylsulfonyl)pyridin-3-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-242
1-((4,4-difluorocyclohexyl)methyl)-4-methyl-N-(5-sulfamoylpyridin-3-yl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-243
1-((4,4-difluorocyclohexyl)methyl)-4-methyl-N-(6-sulfamoylpyridin-2-yl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-244
1-(cyclohexylmethyl)-3-methyl-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamide;
SC-246
3-cyclopropyl-1-((4,4-difluorocyclohexyl)methyl)-N-(2-sulfamoylpyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-247
5-(1-((3,3-difluorocyclopentyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)nicotinamide;
SC-248
4-(1-((3,3-difluorocyclopentyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)pyrimidine-2-carboxamide;
SC-249
4-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)-5-methylpicolinamide;
SC-250
3-cyclopropyl-1-((4,4-difluorocyclohexyl)methyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-251
5-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)-2-methylnicotinamide;
SC-252
1-((4,4-difluorocyclohexyl)methyl)-3-methyl-N-(2-methylpyridin-4-yl)-4-(trifluoromethyl)-
lH-pyrazole-5-carboxamide;
SC-253
6-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-254
1-((3,3-difluorocyclopentyl)methyl)-4-methyl-N-(2-sulfamoylpyridin-4-yl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-255
1-((1-hydroxycyclohexyl)methyl)-N-(3-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamide;
SC-256
2-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)oxazole-5-carboxamide;
SC-257
5-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-258
4-(3-cyclopropyl-1-((tetrahydro-2H-pyran-2-yl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-259
3-cyclopropyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((tetrahydro-2H-pyran-2-yl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-260
4-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)-N-methylpicolinamide;
SC-261
4-(4-chloro-3-cyclopropyl-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-262
1-((3,3-difluorocyclopentyl)methyl)-3-(difluoromethyl)-N-(3-sulfamoylphenyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-263
3-cyclopropyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((tetrahydrofuran-2-yl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-264
3-cyclopropyl-N-(3-sulfamoylphenyl)-1-((tetrahydro-2H-pyran-2-yl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-265
1-((3,3-difluorocyclopentyl)methyl)-3-methoxy-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)-
1H-pyrazole-5-carboxamide;
SC-266
4-(3-cyclopropyl-1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-267
4-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)-6-methylpicolinamide;
SC-268
2-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)-5-fluoroisonicotinamide;
SC-269
4-(1-((3,3-difluorocyclopentyl)methyl)-4-methoxy-3-(trifluoromethyl)-lH-pyrazole-5-
carboxamido)picolinamide;
SC-271
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methoxy-1H-pyrazole-5-
carboxamido)picolinamide;
SC-273
4-(1-((3,3-difluorocyclopentyl)methyl)-3-methoxy-4-(trifluoromethyl)-lH-pyrazole-5-
carboxamido)picolinamide;
SC-274
N-(3-carbamoyl-4-fluorophenyl)-3-cyclopropyl-1-((3,3-difluorocyclobutyl)methyl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-275
3-cyclopropyl-1-((3,3-difluorocyclopentyl)methyl)-4-(difluoromethyl)-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-276
3-cyclopropyl-1-((3,3-difluorocyclobutyl)methyl)-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)-
lH-pyrazole-5-carboxamide;
SC-277
3-cyclopropyl-1-((3,3-difluorocyclopentyl)methyl)-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-278
4-(1-((2,2-difluorocyclobutyl)methyl)-4-methyl-3-(perfluoroethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-279
4-(3-cyclopropyl-1-((2,2-difluorocyclopropyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-280
1-((4,4-difluorocyclohexyl)methyl)-3-methyl-N-(6-(methylsulfonyl)pyridazin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-281
4-(3-cyclopropyl-1-((3-methoxycyclobutyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-282
3-cyclopropyl-1-((3,3-difluorocyclobutyl)methyl)-N-(2-sulfamoylpyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-283
4-(3-(3,3-difluorocyclobutoxy)-1-((3,3-difluorocyclopentyl)methyl)-4-(trifluoromethyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-284
4-(3-cyclopropyl-4-(trifluoromethyl)-1-((5-(trifluoromethyl)tetrahydrofuran-2-yl)methyl)-1H-
pyrazole-5-carboxamido)picolinamide;
SC-286
3-cyclopropyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((5-methyltetrahydrofuran-2-yl)methyl)-
4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-289
4-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)-3-fluoropicolinamide;
SC-290
3-cyclopropyl-1-((3-(difluoromethoxy)cyclobutyl)methyl)-N-(2-(methyIsulfonyl)pyridin-4-
yl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-291
4-(3-cyclopropyl-1-((2,2,3,3-tetrafluorocyclobutyl)methyl)-4-(trifluoromethyl)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-293
1-((3,3-difluorocyclopentyl)methyl)-3-(difluoromethoxy)-N-(2-(methylsulfonyl)pyridin-4-yl)-
4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-294
4-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)-3-methylpicolinamide;
SC-295
1-((3,3-difluorocyclobutyl)methyl)-3-(l,1-difluoroethyl)-4-methyl-N-(3-sulfamoylphenyl)-
lH-pyrazole-5-carboxamide;
SC-296
1-((3,3-difluorocyclopentyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-N-(3-sulfamoylphenyl)-
lH-pyrazole-5-carboxamide;
SC-297
1-((3,3-difluorocyclopentyl)methyl)-3-ethyl-N-(2-(methylsulfonyl)pyridin-4-yl)-4-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-298
4-(3-cyclopropyl-1-((3,3-difluorocyclopentyl)methyl)-4-(2,2,2-trifluoroethoxy)-1H-pyrazole-
5-carboxamido)picolinamide;
SC-299
4-(1-((3,3-difluoro-1-(trifluoromethyl)cyclobutyl)methyl)-3-(1,1-difluoroethyl)-4-methyl-1H-
pyrazole-5-carboxamido)picolinamide;
SC-301
4-(3-(1,1-difluoroethyl)-1-((3-fluorocyclobutyl)methyl)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-302
1-((3,3-difluorocyclobutyl)methyl)-3-ethyl-4-methyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1H-
pyrazole-5-carboxamide;
SC-303
1-((3,3-difluorocyclobutyl)methyl)-3-(l,1-difluoroethyl)-N-(2-(methylsulfinyl)pyridin-4-yl)-
4-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-304
1-((3,3-difluorocyclopentyl)methyl)-3-methyl-N-(3-sulfamoylphenyl)-4-(trifluoromethoxy)-
lH-pyrazole-5-carboxamide;
SC-305
3-cyclopropyl-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-4-
(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxamide;
SC-308
3-(1,1-difluoroethyl)-1-((1-methoxycyclopropyl)methyl)-4-methyl-N-(2-sulfamoylpyridin-4-
yl)-1H-pyrazole-5-carboxamide;
SC-309
4-(1-((3,3-difluorocyclobutyl)methyl)-3-(1,1-difluoroethoxy)-4-methyl-1H-pyrazole-5-
carboxamido)picolinamide;
SC-310
3-(1,1-difluoroethyl)-1-((1-fluorocyclopropyl)methyl)-4-methyl-N-(2-sulfamoylpyridin-4-yl)-
lH-pyrazole-5-carboxamide;
SC-311
4-(3-(1,l-difluoroethyl)-1-((1-(difluoromethyl)-3,3-difluorocyclobutyl)methyl)-4-methyl-1H-
pyrazole-5-carboxamido)picolinamide;
SC-312
3-(1,1-difluoroethyl)-4-methyl-1-((2-methyltetrahydro-2H-pyran-2-yl)methyl)-N-(2-
sulfamoylpyridin-4-yl)-1H-pyrazole-5-caiboxamide;
SC-313
3-(1,1-difluoroethyl)-4-methyl-1-((1-methylcyclopropyl)methyl)-N-(2-sulfamoylpyridin-4-
yl)-1H-pyrazole-5-carboxamide;
SC-314
3-(1,1-difluoroethyl)-4-methyl-1-((2-methylcyclopropyl)methyl)-N-(2-sulfamoylpyridin-4-
yl)-1H-pyrazole-5-carboxamide;
SC-315
4-(3-(1,1-difluoroethyl)-4-methyl-1-((2-(trifluoromethyl)cyclobutyl)methyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-316
3-(1,1-difluoroethyl)-1-((1-(difluoromethyl)-3,3-difluorocyclobutyl)methyl)-4-methyl-N-(2-
sulfamoylpyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-317
3-(1,1-difluoroethyl)-4-methyl-1-((2-methyloxetan-2-yl)methyl)-N-(2-sulfamoylpyridin-4-yl)-
lH-pyrazole-5-carboxamide;
SC-318
4-(1-((3,3-difluorocyclobutyl)methyl)-4-methyl-3-(trifluoromethoxy)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-319
3-(1,1-difluoroethyl)-4-methyl-1-((2-methyltetrahydrofuran-2-yl)methyl)-N-(2-
sulfamoylpyridin-4-yl)-1H-pyrazole-5-caiboxamide;
SC-320
1-((4,4-difluorocyclohexyl)methyl)-4-methyl-N-(2-sulfamoylpyridin-4-yl)-3-
(trifluoromethyl)-1H-pyrazole-5-carboxamide;
SC-321
5-(1-((4,4-difluorocyclohexyl)methyl)-3-methyl-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)pyridazine-3-carboxamide;
SC-322
3-cyclopropyl-4-(difluoromethoxy)-N-(2-(methylsulfonyl)pyridin-4-yl)-1-((tetrahydro-2H-
pyran-4-yl)methyl)-1H-pyrazole-5-carboxamide;
SC-323
1-((3,3-difluorocyclobutyl)methyl)-3-(difluoromethoxy)-4-methyl-N-(2-
(methylsulfonyl)pyridin-4-yl)-1H-pyrazole-5-carboxamide;
SC-324
4-(1-((3,3-difluorocyclobutyl)methyl)-3-(difluoromethyl)-4-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)picolinamide;
SC-325
4-(1-((3,3-difluorocyclopentyl)methyl)-3-(difluoromethyl)-4-(trifluoromethyl)-lH-pyrazole-5-
carboxamido)picolinamide;
in the form of the free compound or a physiologically acceptable salt thereof.

827 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/840,712Filed 15 Jun 2022 · us provisional application
Priority: EP 2117963615 Jun 2021
Published: US 2023/0025025 A126 Jan 2023
Granted: 4 Jun 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 231/14
Having two or three double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having…
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07D 231/20
One oxygen or sulfur atom: one oxygen atom attached in position 3 or 5
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

Application63/210,607Us provisional application · filed 15 Jun 2021
Application63/273,417Us provisional application · filed 29 Oct 2021
Application63/341,107Us provisional application · filed 12 May 2022
US 2023/0025025 A1Pre-grant publication · published 26 Jan 2023
US 11,999,699 B2This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

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Abstract

The present invention relates to compounds according to general formula (I) which act as inhibitors of NaV1.8 and can be used in the treatment of pain.

A compound according to general formula (I)

wherein
L represents CH2, CH(CH3) or CH(CH2CH3);
R1 represents C3-10-cycloalkyl, or 4 to 10-membered heterocycloalkyl,
R2 represents H or C1-6-alkyl;
X represents phenyl, or 5 to 10-membered heteroaryl;
R3 represents S(O)2—C1-6-alkyl, S(O)2—(C3-6-cycloalkyl), S(O)2-(4 to 6-membered heterocycloalkyl), S(O)2-phenyl, S(O)2-(5 or 6-membered heteroaryl), S(O)—NH2, S(O)—N(H)(C1-6-alkyl), S(O)—N(C1-6-alkyl)2, S(O)2—NH2, S(O)2—N(H)(C1-6-alkyl), S(O)2—N(H)(C3-6-cycloalkyl), S(O)2—N(C1-6-alkyl)2, C(O)—NH2, C(O)—N(H)(C1-6-alkyl), C(O)—N(H)(C3-6-cycloalkyl), C(O)—N(C1-6-alkyl)2, C(O)—N(C1-6-alkyl)(C3-6-cycloalkyl), OCF3, OCF2H, CN, OH, O—C3-6-cycloalkyl, O-(4 to 6-membered heterocycloalkyl), S(O)—C1-6-alkyl, S(O)—(C3-6-cycloalkyl), S(O)-(4 to 6-membered heterocycloalkyl), S(O)-phenyl, or S(O)-(5 or 6-membered heteroaryl);
R4 and R5 independently from one another represent H, F, Cl, Br, CN, CHF2, CH2F, CF3, C1-6-alkyl, C3-10-cycloalkyl, C1-6-alkylene-C3-10-cycloalkyl, 4 to 10-membered heterocycloalkyl, C1-6-alkylene-(4 to 10-membered heterocycloalkyl), NH2, N(H)(C1-6-alkyl), N(C1-6-alkyl)2, O—C1-6-alkyl, O—C3-10-cycloalkyl, O—C1-6-alkylene-C3-10-cycloalkyl, O-(4 to 6-membered heterocycloalkyl), or O—C1-6-alkylene-(4 to 6-membered heterocycloalkyl), provided that at least one of R4 and R5 does not represent H;
wherein C1-6-alkyl and C1-6-alkylene in each case independently from one another is linear or branched;
wherein C1-6-alkyl, C1-6-alkylene, C3-10-cycloalkyl, C3-6-cycloalkyl, 4 to 10-membered heterocycloalkyl and 4 to 6-membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with F;
and/or are unsubstituted or monosubstituted with one substituent selected from the group consisting of Cl, CN, C1-6-alkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, CF3, CF2H, CFH2, C(O)—C1-6-alkyl, OH, ═O, OCF3, OCF2H, OCFH2, O—C1-6-alkyl, C1-4-alkylene-O—C1-4-alkylene-O—CH3, and C0-4-alkylene-O—(C1-4-alkylene-O)1-4—CH3;
wherein phenyl, 5 to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from the group consisting of F, Cl, Br, CN, C1-6-alkyl, C3-6-cycloalkyl, CF3, CF2H, CFH2, C1-6-alkylene-CF3, C1-6-alkylene-CF2H, C1-6-alkylene-CFH2, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C(O)—C1-6-alkyl, OCF3, OCF2H, OCFH2, and O—C1-6-alkyl;
in the form of the free compound or a physiologically acceptable salt thereof.

9 more elements

Facts

Application

17/840,712Filed 15 Jun 2022 · us provisional application

Priority

EP 2117963615 Jun 2021

Published

US 2023/0025025 A126 Jan 2023

Granted

4 Jun 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 231/14
Having two or three double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having…
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07D 231/20
One oxygen or sulfur atom: one oxygen atom attached in position 3 or 5
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

Application63/210,607Us provisional application · filed 15 Jun 2021

Application63/273,417Us provisional application · filed 29 Oct 2021

Application63/341,107Us provisional application · filed 12 May 2022

US 2023/0025025 A1Pre-grant publication · published 26 Jan 2023

US 11,999,699 B2This patent

From the US filing history. Foreign family members aren’t listed.