Claims for Patent: 10,214,509

Summary for Patent: 10,214,509

Title:	Amino-substituted heterocyclic derivatives as sodium channel inhibitors
Abstract:	The present invention relates to novel aminoindazolyl derivative compounds of Formula (I), the use of said compounds in treating diseases mediated by modulation of voltage-gated sodium channels in particular Nav1.7 AND to compositions containing said derivatives. ##STR00001##
Inventor(s):	Duffy; James (Saffron Walden Essex, GB), Chambers; Mark Stuart (Saffron Walden Essex, GB), Rae; Alastair (Saffron Walden Essex, GB), Osborne; James (Saffron Walden Essex, GB), Lemasson; Isabelle Anne (Saffron Walden Essex, GB), Goldsmith; Michael Daniel (Saffron Walden Essex, GB), Sharpe; Andrew (Saffron Walden Essex, GB), Fonquerna Pou; Silvia (Barcelona, ES)
Assignee:	Almirall, S.A. (Barcelona, ES)
Application Number:	15/567,668
Patent Claims:	1. A compound of Formula (I), or a pharmaceutically acceptable salt, N-oxide, or isotopically-labeled derivative thereof: ##STR00024## wherein: G.sub.1 is --N-- or --CH--; G.sub.2 is --N-- or --CR.sub.1, wherein R.sub.1 is chosen from a hydrogen atom and a linear or branched C.sub.1-4 alkyl group, with the proviso that at least one of G.sub.1 and G.sub.2 is --N--; R.sub.2 is a is a hydrogen atom and R.sub.3 is a group of Formula (i): ##STR00025## wherein each G.sub.3 is independently --N-- or --CR.sub.7, wherein R.sub.7 is chosen from a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a phenyl group, a linear or branched CIA alkyl group, a linear or branched (C.sub.1-4 alkoxy)-(C.sub.1-4 alkyl) group, --O--(CH.sub.2).sub.1-2--NR.sup.aR.sup.b, --NR.sup.aR.sup.b, --CO--NR.sup.aR.sup.b, --OR.sup.c and --CH.sub.2--R.sup.d; R.sub.6 is chosen from a halogen atom, a cyano group, a linear or branched C.sub.1-4 alkyl group, a lineal linear or branched C.sub.1-4 haloalkyl group, a linear or branched C.sub.1-4 haloalkoxy group, --SO.sub.2--CF.sub.3 group, a O-phenyl group, a benzyl group and a --O-benzyl group; or R.sub.2 and R.sub.3 together with the nitrogen atom to which they are attached form the group of Formula (ii): ##STR00026## wherein each G.sub.4 is independently --CR.sup.8-- or --N--, wherein R.sup.8 is chosen from a hydrogen atom and a halogen atom; R.sub.4 is chosen from a halogen atom, a hydroxyl group, a linear or branched C.sub.1-4 alkyl group, a linear or branched C.sub.1-4 haloalkyl group, a linear or branched (C.sub.1-4 alkyl)-(C.sub.1-4 alkoxy) group, a linear or branched (C.sub.1-4 alkoxy)-(C.sub.1-4 alkyl) group, a linear or branched (C.sub.1-4 alkoxy)-(C.sub.1-4 alkoxy) group, --O.sub.(0-1)(CH.sub.2).sub.(0-2)--NR.sup.aR.sup.b group, --O--(CH.sub.2).sub.(0-2)R.sup.c group, --O--(CHR.sup.f).sub.1--CO--NR.sup.aR.sup.b group, --SO.sub.2--NR.sup.aR.sup.b group, a C.sub.6-6 aryl group, a monocyclic 5- to 8-membered heteroaryl group containing at least one heteroatom chosen from N, O and S, wherein the heteroaryl ring is optionally substituted with one or more substituents chosen from a halogen atom, a C.sub.1-2 alkyl group, a C.sub.1-2 alkoxy group and amino group optionally substituted with one or two C.sub.1-2 alkyl groups, and a 4- to 6-membered saturated or non-saturated heterocyclyl group containing at least one heteroatom chosen from N, O and S, wherein the heterocyclyl ring is optionally substituted with one or more substituents chosen from a C.sub.1-2 alkyl group, a C.sub.1-2 alkoxy group and --C(O)O--R.sup.e group, wherein R.sup.e represents a linear or branched C.sub.1-4 alkyl group, and wherein R.sup.f is a hydrogen atom, a halogen atom or a linear or branched C.sub.1-4 alkyl group; R.sub.5 is chosen from a hydrogen atom, a halogen atom, a linear or branched C.sub.1-4 alkyl group and a linear or branched C.sub.1-4 haloalkyl group; R.sup.a and R.sup.b are independently chosen from a hydrogen atom, a linear or branched C.sub.1-4 alkyl group, a linear or branched (C.sub.1-4 alkoxy)-(C.sub.1-4 alkyl) group and a 5- to 8-membered monocyclic heteroaryl group containing at least one heteroatom chosen from N, S and O, or R.sup.a and R.sup.b together with nitrogen atom to which they are attached form a 3- to 6-membered heterocyclyl group optionally containing a further heteroatom chosen from N, S and O, wherein the heterocyclyl group is optionally substituted with one or more substituents chosen from a C.sub.1-2 alkyl group; R.sup.c is chosen from a linear or branched C.sub.1-4 alkyl group, a linear or branched C.sub.1-4 hydroxyalkyl group, a linear or branched C.sub.1-4 haloalkyl group, a linear or branched (C.sub.1-4 alkoxy)-(C.sub.1-4 alkyl) group, a linear or branched (C.sub.1-4 alkyl)-(C.sub.1-4 alkoxy) group, a C.sub.6-8 aryl group, a monocyclic 5- to 8-membered heteroaryl group containing at least one heteroatom chosen from N, O and S, and a 4- to 6-membered heterocyclyl group containing at least one heteroatom chosen from N, O and S, wherein the heterocyclyl ring is optionally substituted with one or more substituents chosen from a C.sub.1-2 alkyl group and a C.sub.1-2 alkoxy group; R.sup.d is chosen from --NR.sup.aR.sup.b group, a 4- to 6-membered heterocyclyl group containing at least one heteroatom chosen from N, O and S, wherein the heterocyclyl group is optionally substituted with one or more substituents chosen from a halogen atom; with the proviso that the compound is not chosen from: 5-amino-N-(4-ethylphenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxam- ide, 5-amino-N-(2,4-dimethylphenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4- -carboxamide, 5-amino-1-(2,5-dimethylphenyl)-N-(4-fluorophenyl)-1H-1,2,3-triazole-4-car- boxamide, 5-amino-N-(2,4-dichlorophenyl)-1-(2-methylphenyl)-1H-1,2,3-triaz- ole-4-carboxamide, 5-amino-1-(2-methylphenyl)-N-(4-methylphenyl)-1H-1,2,3-triazole-4-carboxa- mide, 5-amino-N-(4-chlorophenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-ca- rboxamide, 5-amino-N-(4-fluorophenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole- -4-carboxamide, 5-amino-N-(4-bromophenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole-4-carboxa- mide, 5-amino-N-(2,4-difluorophenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole- -4-carboxamide, 5-amino-1-(2-methoxyphenyl)-N-(4-methylphenyl)-1H-1,2,3-triazole-4-carbox- amide, and 5-amino-N-(4-fluorophenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazol- e-4-carboxamide. 2. The compound according to claim 1, wherein R.sub.6 is chosen from a halogen atom, a cyano group, a linear or branched C.sub.1-4 alkyl group, a linear or branched C.sub.1-4 haloalkyl group, a linear or branched C.sub.1-4 haloalkoxy group, --SO.sub.2--CF.sub.3 group, a benzyl group and --O-benzyl group; and R.sup.f is a linear or branched C.sub.1-4 alkyl group. 3. The compound according to claim 1, wherein, in Formula (ii), G.sub.4 is a --CR.sup.8, wherein R.sup.8 is chosen from a hydrogen atom and a halogen atom. 4. The compound according to claim 1, wherein R.sub.2 is a hydrogen atom and R.sub.3 is a group of Formula (i), wherein each G.sub.3 s independently --N-- or --CR.sub.7, wherein R.sub.7 is chosen from a hydrogen atom, a cyano group, a linear or branched C.sub.1-4 alkyl group, a (C.sub.1-2 alkoxy)-(C.sub.1-2 alkyl) group, and --OR.sup.c, wherein R.sup.c is chosen from a C.sub.1-2 alkyl group and a C.sub.1-2 haloalkyl group. 5. The compound according to claim 4, wherein R.sub.2 is a hydrogen atom and R.sub.3 is a group of Formula (i), wherein G.sub.3 is a --N-- group. 6. The compound according to claim 4, wherein R.sub.2 is a hydrogen atom and R.sub.3 is a group of Formula (i), wherein one G.sub.3 is a --N-- group and the other G.sub.3 is a --CR.sub.7 group. 7. The compound according to claim 1, wherein R.sub.6 is selected chosen from a halogen atom, a cyano group, a linear or branched C.sub.1-4 alkyl group, a linear or branched C.sub.1-4 haloalkyl group and a linear or branched C.sub.1-4 haloalkoxy group. 8. The compound according to claim 7, wherein R.sub.6 is chosen from a chlorine, a bromine atom, a methyl group, an ethyl group and a --CF.sub.3 group. 9. The compound according to claim 1, wherein both G.sub.1 and G.sub.2 are --N-- group. 10. The compound according to claim 1, wherein G.sub.1 is a --N-- group while G.sub.2 is a --CR.sub.1-- group, wherein R.sub.1 is chosen from a hydrogen atom, a methyl group and an ethyl group. 11. The compound according to claim 1, wherein R.sub.4 is chosen from a halogen atom, a hydroxyl group, a linear or branched C.sub.1-4 alkyl group, a linear or branched C.sub.1-4 haloalkyl group, a C.sub.6-8 aryl group, --O.sub.(0-1)--(CH.sub.2).sub.(O-2)--NR.sup.aR.sup.b group, --O-- (CH.sub.2).sub.(0-2)R.sup.c group, --O--(CH.sub.2).sub.1--CO--NR.sup.aR.sup.b group, wherein R.sup.a and R.sup.b are independently chosen from a hydrogen atom and a linear or branched C.sub.1-4 alkyl group, and wherein R.sup.c is chosen from a linear or branched C.sub.1-4 alkyl group, a linear or branched (C.sub.1-4 alkoxy)-(C.sub.1-4 alkyl) group, and a linear or branched C.sub.1-4 haloalkyl group. 12. The compound according to claim 11, wherein R.sub.4 is chosen from a fluorine atom, a hydroxyl group, a methyl group, --O--R.sup.c group and --O--(CH.sub.2).sub.1--CO--NR.sup.aR.sup.b group, wherein both R.sup.a and R.sup.b are hydrogen and wherein R.sup.c is selected chosen from a methyl group and a methoxyethyl group. 13. The compound according to claim 1, wherein R.sub.5 is chosen from a hydrogen atom and a halogen atom. 14. The compound according to claim 1, having the following Formula (II) ##STR00027## wherein: R.sub.1 is chosen from a hydrogen atom, a methyl group and an ethyl group; R.sub.4 is chosen from a fluorine atom, a hydroxyl group, a methyl group, a --O--R.sup.c group and a --O--(CH.sub.2).sub.1--CO--NR.sup.aR.sup.b group, wherein both R.sup.a and R.sup.b are hydrogen and wherein R.sup.c is chosen from a methyl group and a methoxyethyl group; R.sub.5 is chosen from a hydrogen atom and a fluorine atom; R.sub.6 is chosen from a chlorine atom, a methyl group and a --CF.sub.3 group. 15. The compound according to claim 1, wherein the compound is chosen from: 5-Amino-N-(4-chlorophenyl)-1-(2-methoxyphenyl)-1H-pyrazole-4-carbox- amide, 5-Amino-N-(4-bromophenyl)-1-(2-methoxyphenyl)-1H-pyrazole-4-carboxa- mide, 5-Amino-1-(2-methoxyphenyl)-N-(p-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(o-tolyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazole-4-car- boxamide, 5-Amino-N-(4-chloro-2-methyl-phenyl)-1-(o-tolyl)-1H-pyrazole-4-c- arboxamide, 5-Amino-N-(4-chloro-2-fluoro-phenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxamid- e, 5-Amino-N-(4-chloro-2-cyano-phenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxami- de, 5-Amino-N-(4-chloro-2-methoxy-phenyl)-1-(o-tolyl)-1H-pyrazole-4-carbox- amide, 5-Amino-N-(5-chloro-3-methyl-2-pyridyl)-1-(o-tolyl)-1H-pyrazole-4-c- arboxamide, 5-Amino-N-[3-fluoro-5-(trifluoromethyl)-2-pyridyl]-1-(o-tolyl)-1H-pyrazol- e-4-carboxamide, 5-Amino-N-(5-chloro-3-methoxy-2-pyridyl)-1-(o-tolyl)-1H-pyrazole-4-carbox- amide, 5-Amino-N-(4-chloro-2-(methylamino)phenyl)-1-(o-tolyl)-1H-pyrazole-- 4-carboxamide, 5-Amino-N-(2-carbamoyl-4-chlorophenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxam- ide, 5-Amino-N-(2-cyano-4-(trifluoromethyl)phenyl)-1-(o-tolyl)-1H-pyrazole- -4-carboxamide, 5-Amino-N-(2-methoxy-4-(trifluoromethyl)phenyl)-1-(o-tolyl)-1H-pyrazole-4- -carboxamide, 5-Amino-N-(4-chloro-2-hydroxyphenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxamid- e, 5-Amino-N-(4-chloro-2-((dimethylamino)methyl)phenyl)-1-(o-tolyl)-1H-pyr- azole-4-carboxamide, 5-Amino-N-(4-chloro-2-(methoxymethyl)phenyl)-1-(o-tolyl)-1H-pyrazole-4-ca- rboxamide, 5-Amino-N-(4-bromo-2-methoxy-phenyl)-1-(o-tolyl)-1H-pyrazole-4-- carboxamide, 5-Amino-N-(4-chloro-2-fluoro-phenyl)-1-[2-(2-methoxyethoxy)phenyl]-1H-pyr- azole-4-carboxamide, 5-Amino-N-(4-chloro-2-methoxy-phenyl)-1-[2-(2-methoxyethoxy)phenyl]-1H-py- razole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-[2-(2-methoxyethoxy)phenyl]-1H-pyrazole-- 4-carboxamide, 5-Amino-N-[4-chloro-2-[[isopropyl(methyl)amino]methyl]phen y]-1-(o-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-[4-chloro-2-(pyrrolidin-1-ylmethyl)phenyl]-1-(o-tolyl)-1H-pyraz- ole-4-carboxamide, 5-Amino-N-[4-chloro-2-(morpholinomethyl)phenyl]-1-(o-tolyl)-1H-pyrazole-4- -carboxamide, 5-Amino-N-(4-cyanophenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(4-tert-butylphenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-[4-chlor-2-[[(3R)-3-fluoropyrrolidin-1-yl]methyl]phenyl]-1-(o-t- olyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(4-chloro-2-phenyl-phenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxamid- e, 5-Amino-1-[2-(2-methoxyethoxy)phenyl]-N-[4-(trifluoromethyl)phenyl]-1H-- pyrazole-4-carboxamide, 5-Amino-N-[2-fluoro-4-(trifluoromethyl)phenyl]-1-[2-(2-methoxyethoxy)phen- yl]-1H-pyrazole-4-carboxamide, 5-Amino-N-(2-bromo-4-chloro-phenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide- , 5-Amino-1-[2-(2-methoxyethoxy)phenyl]-N-[2-methyl-4-(trifluoromethyl)phe- nyl]-1H-pyrazole-4-carboxamide, 5-Amino-N-(4-chloro-2-methoxy-phenyl)-3-methyl-1-(o-tolyl)-1H-pyrazole-4-- carboxamide, 5-Amino-N-(4-chloro-2-methoxy-phenyl)-1-[2-(2-methoxyethoxy)phenyl]-3-met- hyl-1H-pyrazole-4-carboxamide, 5-Amino-1-[2-(2-methoxyethoxy)phenyl]-N-[2-methoxy-4-(trifluoromethyl)phe- nyl]-3-methyl-1H-pyrazole-4-carboxamide, 5-Amino-N-(2-fluoro-4-(trifluoromethyl)phenyl)-1-(2-(2-methoxyethoxy)phen- yl)-3-methyl-1H-pyrazole-4-carboxamide, 5-Amino-N-[2-cyano-4-(trifluoromethyl)phenyl]-1-(2-ethylphenyl)-3-methyl-- 1H-pyrazole-4-carboxamide, 5-Amino-N-(4-bromo-2-methoxy-phenyl)-1-(2-ethylphenyl)-3-methyl-1H-pyrazo- le-4-carboxamide, 5-Amino-N-(4-chloro-2-methoxy-phenyl)-1-(2-ethylphenyl)-3-methyl-1H-pyraz- ole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(2-ethylphenyl)-3-methyl-1H-pyrazole-4-c- arboxamide, 5-Amino-N-(4-chloro-2-fluoro-phenyl)-1-[2-(2-methoxyethoxy)phenyl]-3-meth- yl-1H-pyrazole-4-carboxamide, 5-Amino-N-[2-fluoro-4-(trifluoromethyl)phenyl]-3-methyl-1-(o-tolyl)-1H-py- razole-4-carboxamide, 5-Amino-1-(2-ethylphenyl)-3-methyl-N-[5-(trifluoromethyl)-2-pyridyl]-1H-p- yrazole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-[2-(2-methoxyethoxy)phenyl]-3-methyl-1H-- pyrazole-4-carboxamide, 5-Amino-1-(o-tolyl)-N-[4-(trifluoromethylsulfonyl)phenyl]-1H-pyrazole-4-c- arboxamide, 5-Amino-N-[4-bromo-2-(difluoromethoxy)phenyl]-1-(o-tolyl)-1H-pyrazole-4-c- arboxamide, 5-Amino-N-(4-chloro-2-fluoro-phenyl)-3-methyl-1-(o-tolyl)-1H-pyrazole-4-c- arboxamide, 5-Amino-N-(5-methylpyridin-2-yl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-cyanopyridin-2-yl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-bromopyridin-2-yl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(o-tolyl)-N-(5-(trifluoromethoxy)pyridin-2-yl)-1H-pyrazole-4-ca- rboxamide, 5-Amino-1-(2-methoxyphenyl)-N-[5-(2,2,2-trifluoroethoxy)-2-pyri- dyl]pyrazol e-4-carboxamide, 5-Amino-1-(3-fluoro-2-methylphenyl)-N-(5-(trifluoromethoxy)pyridin-2-yl)-- 1H-pyrazole-4-carboxamide, 5-Amino-N-(5-bromopyridin-2-yl)-1-(2-fluorophenyl)-1H-pyrazole-4-carboxam- ide, (5-Amino-1-(3-fluoro-2-methylphenyl)-1H-pyrazol-4-yl)(5-chloroindolin- -1-yl)methanone, 5-Amino-1-(3-fluoro-2-methylphenyl)-N-(4-(trifluoromethyl)phenyl)-1H-pyra- zole-4-carboxamide, (5-Amino-1-(o-tolyl)-1H-pyrazol-4-yl)(5-chloroindolin-1-yl)methanone, [5-Amino-1-(2-fluorophenyl)pyrazol-4-yl](5-chloroindolin-1-yl)methanone, (5-Amino-1-(2-methoxyphenyl)-H-pyrazol-4-yl)(5-chloroindolin-1-yl)methano- ne, 5-Amino-N-(4-bromophenyl)-1-(o-tolyl)-1H-1,2,3-triazole-4-carboxamide, 5-Amino-1-(2-methoxyphenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-1,2,3-- triazole-4-carboxamide, 5-Amino-1-(2-methoxyphenyl)-N-(p-tolyl)-1H-1,2,3-triazole-4-carboxamide, 5-Amino-1-(2-methoxyphenyl)-N-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazo- le-4-carboxamide, 5-Amino-1-(2-methoxyphenyl)-N-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triaz- ole-4-carboxamide, 5-Amino-N-(4-isopropylphenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole-4-car- boxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-methoxyphenyl)-1H-1,2,3-tr- iazole-4-carboxamide, 5-Amino-1-(2-methoxyphenyl)-N-(4-phenoxyphenyl)-1H-1,2,3-triazole-4-carbo- xamide, 5-Amino-1-(2-methoxyphenyl)-N-(4-(1,1,2,2-tetrafluoroethoxy)phenyl- )-1H-1,2,3-triazole-4-carboxamide, 5-Amino-N-(4-(benzyloxy)phenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole-4-c- arboxamide, 5-Amino-N-(4-benzylphenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole-4-carbox- amide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(o-tolyl)-1H-1,2,3-triazole-4-ca- rboxamide, 5-Amino-1-(o-tolyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-1,2,- 3-triazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(3-fluoro-2-methylphenyl)-1H-1,2,3-tri- azole-4-carboxamide, 5-Amino-1-(3-fluoro-2-methylphenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1- H-1,2,3-triazole-4-carboxamide, 5-Amino-N-(4-chlorophenyl)-1-(2,6-dimethylphenyl)-1H-pyrazole-4-carboxami- de, 5-Amino-1-(2-chlorophenyl)-N-(4-chlorophenyl)pyrazole-4-carboxamide, 5-Amino-N-(4-chlorophenyl)-1-(o-tolyl)pyrazole-4-carboxamide, 5-Amino-N-(4-chlorophenyl)-1-[2-(trifluoromethyl)phenyl]pyrazole-4-carbox- amide, 5-Amino-N-(4-chlorophenyl)-1-(2,3-dichlorophenyl)-1H-pyrazole-4-car- boxamide, 5-Amino-N-(4-chlorophenyl)-1-(2-fluorophenyl)pyrazole-4-carboxam- ide, 5-Amino-N-(4-chlorophenyl)-1-[3-(trifluoromethyl)phenyl]pyrazole-4-ca- rboxamide, 5-Amino-1-(2-ethylphenyl-N-[5-trifluoromethyl-2-pyridyl]pyrazol- e-4-carboxamide, 5-Amino-1-(2-chlorophenyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazole-4-carb- oxamide, 5-Amino-1-(2-isopropylphenyl)-N-[5-trifluoromethyl-2-pyridyl]pyra- zole-4-carboxamide, 5-Amino-1-[2-(trifluoromethoxy)phenyl]-N-[5-trifluoromethyl-2-pyridyl]pyr- azole-4-carboxamide, 5-Amino-1-[2-(2-methoxyethoxy)phenyl]-N-[5-trifluoro methyl-2-pyridyl]pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-ethylphenyl)-1H-pyrazole-4-carboxam- ide, 5-Amino-1-(2-(methoxymethyl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-y- l)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-methoxyphenyl)-1H-pyrazole-4-carbox- amide, 5-Amino-1-(2-chlorophenyl)-N-(5-chloropyridin-2-yl)-1H-pyrazole-4-c- arboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(2-methoxyphenyl)-1H-pyrazole-4-ca- rboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(2-ethylphenyl)-1H-pyraz- ole-4-carboxamide, 1-(2-(1H-Pyrazol-1-yl)phenyl)-5-amino-N-(5-(trifluoromethyl)pyridin-2-yl)- -1H-pyrazole-4-carboxamide, 5-Amino-1-(2-bromophenyl)-N-(5-chloropyridin-2-yl)-1H-pyrazole-4-carboxam- ide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(5-fluoro-2-methylphenyl)-1H-p- yrazole-4-carboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(4-fluoro-2-methylphenyl)-1H-pyraz- ole-4-carboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(3-fluoro-2-methylphenyl)-1H-pyraz- ole-4-carboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(2,3-dimethylphenyl)-1H-pyrazole-4- -carboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(2,5-dimethylphenyl)-1H-pyrazole-4- -carboxamide, 5-Amino-1-(2-bromophenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazole- -4-carboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-(2-chlorophenyl)-1H-pyrazole-4-car- boxamide, 5-Amino-1-(2-methyl-5-(trifluoromethyl)phenyl)-N-(5-(trifluorome- thyl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-[2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-N-[5-trifluoromethyl-- 2-pyridyl]pyrazole-4-carboxamide, 5-Amino-1-(2-fluoro-6-methylphenyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazo- le-4-carboxamide, 5-Amino-1-(2-(oxazol-5-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-- pyrazole-4-carboxamide, 5-Amino-1-[2-(dimethylaminomethyl)phenyl]-N-[5-trifluoromethyl-2-pyridyl]- pyrazole-4-carboxamide, 5-Amino-N-(4-chloro-2-methoxyphenyl)-1-[3-fluoro-2-(2-methoxyethoxy)pheny- l]pyrazole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-[3-fluoro-2-(2-methoxyethoxy)phenyl]-pyr- azole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-[2-(dimethylaminomethyl)-phenyl]-pyrazol- e-4-carboxamide, 5-Amino-1-[3-fluoro-2-(2-methoxyethoxy)phenyl]-N-[5-trifluoromethyl-2-pyr- idyl]pyrazole-4-carboxamide, 5-Amino-1-[3-fluoro-2-(2-methoxyethoxy)phenyl]-3-methyl-N-[5-(trifluorome- thyl)-2-pyridyl]pyrazole-4-carboxamide, 5-Amino-3-ethyl-1-(2-methoxyphenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1- H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-methoxyethoxy)phenyl)-3-methyl-N-(2-methyl-4-(trifluorome- thyl)phenyl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-bromo-3-fluorophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyridy- l]pyrazole-4-carboxamide, 5-Amino-1-(2-bromo-6-fluorophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyridy- l]pyrazole-4-carboxamide, 5-Amino-1-(2-chloro-6-fluorophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyrid- yl]pyrazole-4-carboxamide, 5-Amino-1-(2-bromo-3-fluorophenyl)-N-(5-chloro-2-pyridyl)-3-methyl-pyrazo- le-4-carboxamide, 5-Amino-1-(2-chloro-6-fluorophenyl)-N-(5-chloro-2-pyridyl)-3-methyl-pyraz- ole-4-carboxamide, 5-Amino-1-(2-bromophenyl)-N-(5-chloro-2-pyridyl)-3-methyl-pyrazole-4-carb- oxamide, 5-Amino-1-(3-fluoro-2-methylphenyl)-3-methyl-N-[5-trifluoromethyl- -2-pyridyl]pyrazole-4-carboxamide, 5-Amino-1-(2-methoxyphenyl)-3-methyl-N-[5-trifluoromethyl-2-pyridyl]pyraz- ole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(2-methoxyphenyl)-3-methyl-pyrazole-4-ca- rboxamide, 5-Amino-1-(2-bromo-6-fluorophenyl)-N-[5-trifluoromethyl-2-pyrid- yl]pyrazole-4-carboxamide, 5-Amino-1-(2-chloro-6-fluorophenyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazo- le-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(3-fluoro-2-methylphenyl)-1H-pyrazole-- 4-carboxamide, 5-Amino-1-(2-bromo-6-fluorophenyl)-N-(5-chloro-2-pyridyl)pyrazole-4-carbo- xamide, 5-Amino-1-(2-fluoro-6-methoxyphenyl)-3-methyl-N-[5-trifluoromethyl- -2-pyridyl]pyrazole-4-carboxamide, 5-Amino-1-(2-chloro-3-fluorophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyrid- yl]pyrazole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(2-fluoro-6-methoxyphenyl)-3-meth yl-pyrazole-4-carboxamide, 5-Amino-1-(2-chloro-3-fluorophenyl)-N-(5-chloro-2-pyridyl)-3-methyl-pyraz- ole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(2-fluoro-6-methylphenyl)-3-methyl-pyraz- ole-4-carboxamide, 5-Amino-3-ethyl-1-(o-tolyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazole-4-car- boxamide, 5-Amino-3-ethyl-1-(2-(2-methoxyethoxy)phenyl)-N-(5-(trifluoromet- hyl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-chloro-6-fluorophenyl)-N-(5-chloro-2-pyridyl)pyrazole-4-carb- oxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(3-fluoro-2-methylphenyl)-3-meth- yl-pyrazole-4-carboxamide, 5-Amino-1-(2-ethylphenyl)-N-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-1H- -pyrazole-4-carboxamide, 5-Amino-1-(o-tolyl)-N-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)-1H-pyrazole- -4-carboxamide, 5-Amino-1-(2-ethylphenyl)-N-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)-1H-py- razole-4-carboxamide, 5-Amino-1-(2-(2-methoxyethoxy)phenyl)-N-(5-(2,2,2-trifluoroethoxy)pyridin- -2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(3-fluoro-2-methylphenyl)-N-(5-(2,2,2-trifluoroethoxy)pyridin-2- -yl)-1H-pyrazole-4-carboxamide, 5-Amino-3-ethyl-1-(3-fluoro-2-methylphenyl)-N-[5-trifluoromethyl-2-pyridy- l]pyrazole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-3-ethyl-1-(3-fluoro-2-methylphenyl)pyrazol- e-4-carboxamide, 5-Amino-1-(3-fluoro-2-methylphenyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazo- le-4-carboxamide, 5-Amino-N-(4-chloro-2-fluorophenyl)-1-(2-methoxyphenyl)-1H-pyrazole-4-car- boxamide, 5-Amino-1-(3-fluoro-2-methylphenyl)-N-(5-iodopyridin-2-yl)-1H-py- razole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-fluorophenyl)-1H-pyrazole-4-carboxa- mide, 5-amino-1-(2-fluorophenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-py- razole-4-carboxamide, 5-Amino-3-methyl-1-(2-(oxazol-5-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-- 2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-3-ethyl-1-(2-fluorophenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H- -pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-3-ethyl-1-(2-fluorophenyl)-1H-pyrazole-4- -carboxamide, 5-Amino-1-(2-fluorophenyl)-3-methyl-N-(5-(trifluoromethyl)pyridin-2-yl)-1- H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-fluorophenyl)-3-methyl-1H-pyrazole-- 4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-fluoro-3-methylphenyl)-1H-pyrazole-- 4-carboxamide, 5-Amino-1-(2-fluoro-3-methylphen yl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-iodophenyl)-1H-pyrazole-4-carboxami- de, 5-Amino-N-(5-chloropyridin-2-yl)-1-(3-fluoro-2-(oxazol-5-yl)phenyl)-3-- methyl-1H-pyrazole-4-carboxamide, 5-Amino-1-(3-fluoro-2-(oxazol-5-yl)phenyl)-3-methyl-N-(5-(trifluoromethyl- )pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(3-fluoro-2-(oxazol-5-yl)phenyl)-1H-py- razole-4-carboxamide, 5-Amino-1-(3-fluoro-2-(oxazol-5-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-- 2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-3-ethyl-1-(3-fluoro-2-(oxazol-5-yl)phenyl)-N-(5-(trifluoromethyl)- pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-3-ethyl-1-(2-(oxazol-5-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-2- -yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-iodophenyl)-N-(5-((trifluoromethyl)pyridin-2-yl)-1H-pyrazole- -4-carboxamide, 5-Amino-1-(2-iodophenyl)-3-methyl-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-- pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(oxazol-5-yl)phenyl)-1H-pyrazole-4-- carboxamide, 5-Amino-1-(2-chloro-3-fluorophenyl)-N-(5-chloropyridin-2-yl)-1H-pyrazole-- 4-carboxamide, 5-Amino-1-(2-chloro-3-fluorophenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1- H-pyrazole-4-carboxamide, 5-Amino-1-(2-(5-chlorothiopheN-2-yl)phenyl)-N-(5-(trifluoromethyl)pyridin- -2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(pyrrolidin-1-ylsulfonyl)phenyl)-1H- -pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(N-methyl-N-(pyridin-3-yl)sulfamoyl- )phenyl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-bromophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyridyl]pyrazol- e-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(2-fluoro-6-methylphenyl)pyrazole-4-carb- oxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(2-fluoro-6-methoxyphenyl)pyrazo- le-4-carboxamide, 5-Amino-1-(2-chlorophenyl)-N-(5-chloro-2-pyridyl)-3-methyl-pyrazole-4-car- boxamide, 5-Amino-1-(2-chlorophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyrid- yl]pyrazole-4-carboxamide, 5-Amino-3-methyl-1-(2-morphelinophenyl)-N-[5-trifluoromethyl-2-pyridyl]py- razole-4-carboxamide, 5-Amino-1-(2-bromo-6-fluorophenyl)-N-(5-chloro-2-pyridyl)-3-methyl-pyrazo- le-4-carboxamide, 5-Amino-3-isopropyl-1-(o-tolyl)-N-[5-(trifluoromethyl)-2-pyridyl]pyrazole- -4-carboxamide, 5-Amino-1-(2-fluoro-6-methylphenyl)-3-methyl-N-[5-trifluoromethyl-2-pyrid- yl]pyrazole-4-carboxamide, 5-Amino-1-(2-fluoro-6-methoxyphenyl)-N-[5-trifluoromethyl-2-pyridyl]pyraz- ole-4-carboxamide, 5-Amino-1-[2-(2-methoxyethoxy)phenyl]-3-methyl-N-[5-trifluoromethyl-2-pyr- idyl]pyrazole-4-carboxamide, 5-Amino-1-(3-fluoro-2-methoxyphenyl)-N-[5-trifluoromethyl-2-pyridyl]pyraz- ole-4-carboxamide, 5-Amino-N-(5-chloro-2-pyridyl)-1-(3-fluoro-2-methoxyphenyl)pyrazole-4-car- boxamide, 5-Amino-1-(2,6-difluorophenyl)-N-[5-trifluoromethyl-2-pyridyl]py- razole-4-carboxamide, 5-Amino-1-(2,6-dimethylphenyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazole-4-- carboxamide, 5-Amino-1-(2,6-difluorophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyridyl]py- razole-4-carboxamide, 5-Amino-1-(2,6-dimethylphenyl)-3-methyl-N-[5-trifluoromethyl-2-pyridyl]py- razole-4-carboxamide, 5-Amino-1-(2-chloro-6-methylphenyl)-3-methyl-N-[5-trifluoromethyl-2-pyrid- yl]pyrazole-4-carboxamide, 5-Amino-1-(2,6-dichlorophenyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazole-4-- carboxamide, 5-Amino-1-(2-chloro-6-methylphenyl)-N-[5-trifluoromethyl-2-pyridyl]pyrazo- le-4-carboxamide, 5-Amino-1-(2,6-dichlorophenyl)-3-methyl-N-[5-trifluoromethyl-2-pyridyl]py- razole-4-carboxamide, 5-Amino-1-(2-bromo-3-methylphen yl)-N-(5-chloropyridin-2-yl)-1H-pyrazole-4-carboxamide, 1-([1,1'-Biphenyl]-2-yl)-5-amino-N-(5-chloropyridin-2-yl)-1H-pyrazole-4-c- arboxamide, 5-Amino-1-(2-(2-methoxypyridin-4-yl)phenyl)-N-(5-(trifluoromethyl)pyridin- -2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(pyridin-3-yl)phenyl)-1H-pyrazole-4- -carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(2-methoxypyridin-4-yl)phenyl)-1H-p- yrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(1-methyl-1H-pyrazol-4-yl)phenyl)-1- H-pyrazole-4-carboxamide, 5-Amino-3-methyl-1-(2-(pyridin-3-yl)phenyl)-N-(5-(trifluoromethyl)pyridin- -2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-methoxypyridin-4-yl)phenyl)-3-methyl-N-(5-(trifluoromethy- l)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(pyridin-3-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H- -pyrazole-4-carboxamide, 5-Amino-1-(2-(pyridin-4-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H- -pyrazole-4-carboxamide, 5-Amino-1-(2-(5-fluoropyridin-3-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-- 2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(6-methoxypyridin-3-yl)phenyl)-1H-p- yrazole-4-carboxamide, 1-(2-(1-Pyrazol-4-yl)phenyl)-5-amino-N-(5-chloropyridin-2-yl)-1H-pyrazole- -4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(3-fluoro-2-(2-methoxypyridin-4-yl)phe- nyl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-hydroxyphenyl)-1H-pyrazole-4-carbox- amide, 5-Amino-1-(2-hydroxyphenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1H-- pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-ethoxyphenyl)-1H-pyrazole-4-carboxa- mide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(2-(dimethylamino)ethoxy)pheny- l)-1H-pyrazole-4-carboxamide, (R)-5-Amino-N-(5-chloropyridin-2-yl)-1-(2-((tetrahydrofuraN-3-yl)oxy)phen- yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-((1-methylpiperidiN-4-yl)oxy)phenyl- )-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(benzyloxy)phenyl)-N-(5-chloropyridin-2-yl)-1H-pyrazole-4-ca- rboxamide, 5-Amino-1-(2-isopropoxyphenyl)-N-(5-(trifluoromethyl)pyridin-2-- yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(4-chloro-2-(2-(dimethylamino)ethoxy)phenyl)-1-(o-tolyl)-1H-pyr- azole-4-carboxamide, (R)-5-Amino-N-(4-chloro-2-((tetrahydrofuraN-3-yl)oxy)phenyl)-1-(o-tolyl)-- 1H-pyrazole-4-carboxamide, 5-Amino-N-(4-chloro-2-ethoxyphenyl)-1-(o-tolyl)-1H-pyrazole-4-carboxamide- , 5-Amino-N-(4-chloro-2-(2-methoxyethoxy)phenyl)-1-(o-tolyl)-1H-pyrazole-4- -carboxamide, 5-Amino-N-(4-chloro-2-((1-methylpiperidiN-4-yl)oxy)phenyl)-1-(o-tolyl)-1H- -pyrazole-4-carboxamide, 5-Amino-1-(2-((2-methoxyethyl)amino)phenyl)-N-(5-(trifluoromethyl)pyridin- -2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-((2-methoxyethyl)(methyl)amino)phenyl)-N-(5-(trifluoromethyl- )pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(3-methoxypyrrolidin-1-yl)phenyl)-N-(5-(trifluoromethyl)pyri- din-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(4-methoxypiperidiN-1-yl)phenyl)-N-(5-(trifluoromethyl)pyrid- in-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-((3-methyloxetan-3-yl)methoxy)phenyl)-N-(5-(trifluoromethyl)- pyridin-2-yl)-1H-pyrazole-4-carboxamide, 1-(2-(2-(1H-Imidazol-1-yl)ethoxy)phenyl)-5-amino-N-(5-(trifluoromethyl)py- ridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-((tetrahydro-2H-pyraN-4-yl)oxy)phenyl)-N-(5-(trifluoromethyl- )pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-((tetrahydrofuraN-3-yl)oxy)phenyl)-N-(5-(trifluoromethyl)pyr- idin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-((4-methylmorpholin-2-yl)methoxy)phenyl)-N-(5-(trifluorometh- yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 1-(2-(2-(1H-Pyrazol-1-yl)ethoxy)phenyl)-5-amino-N-(5-(trifluoromethyl)pyr- idin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-((1-methylpiperidin-3-yl)methoxy)phenyl)-N-(5-(trifluorometh- yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-amino-2-oxoethoxy)phenyl)-N-(5-(trifluoromethyl)pyridin-2- -yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-amino-2-oxoethoxy)phenyl)-3-ethyl-N-(5-(trifluoromethyl)p- yridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-amino-2-oxoethoxy)phenyl)-N-(5-(trifluoromethoxy)pyridin-- 2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-amino-2-oxoethoxy)-3-fluorophenyl)-N-(5-(trifluoromethyl)- pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-amino-2-oxoethoxy)phenyl)-N-(5-chloropyridin-2-yl)-3-ethy- l-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-(methylamino)-2-oxoethoxy)phenyl)-N-(5-(trifluoromethyl)p- yridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-((2,2-dimethyl-1,3-dioxolaN-4-yl)methoxy)phenyl)-N-(5-(trifl- uoromethyl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-amino-1-fluoro-2-oxoethoxy)phenyl)-N-(5-(trifluoromethyl)- pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-amino-2-oxoethoxy)phenyl)-3-methyl-N-(5-(trifluoromethyl)- pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2,2,3,3,3-pentafluoropropoxy)phenyl)-N-(5-(trifluoromethyl)- pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2,2,2-trifluoroethoxy)phenyl)-N-(5-(trifluoromethyl)pyridin- -2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-[2-(oxetaN-3-yloxy)phenyl]-N-[5-(trifluoromethyl)pyridin-2-yl]-- 1H-pyrazole-4-carboxamide, 5-Amino-1-[2-[(5-methylisoxazol-3-yl)methoxy]phenyl]-N-[5-(trifluoromethy- l)pyridin-2-yl]-1H-pyrazole-4-carboxamide, 5-Amino-1-[2-(3-methoxypropoxy)phenyl]-N-[5-(trifluoromethyl)pyridin-2-yl- ]-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-hydroxyethoxy)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)- -1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(2-hydroxyethoxy)phenyl)-3-methyl-N-(5-(trifluoromethyl)pyri- din-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-3-ethyl-1-(2-(2-hydroxyethoxy)phenyl)-1H- -pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(2-hydroxyethoxy)phenyl)-1H-pyrazol- e-4-carboxamide, 5-Amino-3-ethyl-1-(2-(2-hydroxyethoxy)phenyl)-N-(5-(trifluoromethyl)pyrid- in-2-yl)-1H-pyrazole-4-carboxamide, 5-Amino-1-(2-(difluoromethoxy)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)- -1H-pyrazole-4-carboxamide, 5-Amino-1-(3-fluoro-2-methylphenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1- H-imidazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(3-fluoro-2-methylphenyl)-1H-imidazole- -4-carboxamide, 5-Amino-N-(4-bromophenyl)-1-(2-methoxyphenyl)-1H-imidazole-4-carboxamide, 5-Amino-N-(4-chlorophenyl)-1-(2-methoxyphenyl)-1H-imidazole-4-carboxamide- , 5-Amino-1-(2-methoxyphenyl)-N-(4-(trifluoromethyl)phenyl)-1H-imidazole-4- -carboxamide, 5-Amino-1-(2-(6-aminopyridin-3-yl)phenyl)-N-(5-chloropyridin-2-yl)-1H-pyr- azole-4-carboxamide, 5-Amino-1-(2-(6-aminopyridin-3-yl)phenyl)-N-(5-(trifluoromethyl)pyridin-2- -yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(6-(dimethylamino)pyridin-3-yl)phen- yl)-1H-pyrazole-4-carboxamide, 5-Amino-N-(5-chloropyridin-2-yl)-1-(2-(5-methoxypyridin-3-yl)phenyl)-1H-p- yrazole-4-carboxamide, 5-Amino-1-(2-(2-(4-methylpiperaziN-1-yl)-2-oxoethoxy)phenyl)-N-(5-(triflu- oromethyl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, tert-Butyl 3-(2-(5-amino-4-((5-chloropyridin-2-yl)carbamoyl)-1H-pyrazol-1-yl)phenyl)- -5,6-dihydropyridine-1(2H)-carboxylate, tert-Butyl 5-(2-(5-amino-4-((5-chloropyridin-2-yl)carbamoyl)-1H-pyrazol-1-yl)phenyl)- -3,4-dihydropyridine-1(2H)-carboxylate, tert-Butyl 4-(2-(5-amino-4-((5-chloropyridin-2-yl)carbamoyl)-1H-pyrazol-1-yl)phenyl)- -5,6-dihydropyridine-1(2H)-carboxylate, 5-Amino-1-(2-(2-oxo-2-(pyrrolidin-1-yl)ethoxy)phenyl)-N-(5-(trifluorometh- yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, 5-amino-1-(2-(N-methyl-N-(pyridin-3-yl)sulfamoyl)phenyl)-N-(5-(trifluorom- ethyl)pyridin-2-yl)-1H-pyrazole-4-carboxamide, or a pharmaceutically acceptable salt, N-oxide, or isotopically-labeled derivative thereof. 16. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable diluent or carrier. 17. A combination product for simultaneous, separate, or sequential use in the treatment of the human or animal body comprising (i) the compound according to claim 1; and (ii) at least one additional compound chosen from: (a) Opioid receptor agonists, (b) Opioid receptor partial agonists, (c) NSAIDS, (d) COX-2 inhibitors, (e) Ion channel modulators, (f) Centrally acting agents, (g) Agents for neuropathic pain, (h) Agents for cancer pain, (i) Anti-fibrotics, (j) Prostacyclin analogues, (k) Endothelin antagonists, (l) Phosphodiesterase V inhibitors, (m) Guanylate cyclase stimulators, (n) Oral and inhaled corticosteroids, (o) Phosphodiesterase IV, (p) Beta2-adrenoceptor agonists, (q) Muscarinic antagonists, (r) Xantines, (s) Mast cell stabilizers, (t) Leukotriene modifiers, (u) Th2 cytokine inhibitors, (v) Thromboxane antagonists/thromboxane synthase inhibitors, (w) Anti-IgE therapy compounds, (x) Histamine antagonists, (y) Antiinflammatory agents, (z) JAK inhibitors, (aa) Syk inhibitors, (ab) Immunosupressants, (ac) Antipruritic agents, and (ad) Anti-tussive agents, Decongestants, Mucolytics, Expectorants, or Proton Pump Inhibitors. 18. A method for treating a subject afflicted with a pathological condition or a disease mediated by modulation of voltage-gated sodium channels in particular Nav1.7 comprising administering to the subject an effective amount of the compound according to claim 1. 19. The method according to claim 18, wherein the pathological condition or disease is chosen from pain, idiopathic couch, chronic cough, cough related to respiratory diseases, respiratory diseases, itch, dermatological diseases, epilepsy, schizophrenia and bipolar disorder. 20. The method according to claim 19, wherein the pain disease is chosen from acute pain, chronic pain, inflammatory pain, visceral pain, nociceptive pain, neurophatic pain, postherpetic pain, trigeminal neuralgia, diabetic neuropathy, chronic back pain, chronic pelvic pain, migraine and pain resulting from cancer and chemotherapy.

Details for Patent 10,214,509

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	March 13, 1924	10,214,509	2036-04-20