Katkere, B., Prabhu, S
If you stop mixing early, the formula has not fully activated
Western blot analysis confirmed substantial reduction of SLC25A39 protein in koSLC25A39 tumors, with no notable change in SLC25A40 expression (Fig
doi: 10.1038/sj.ijo.0802250 149 Di MarzoVGoparajuSKWangLLiuJBtkaiSJraiZet al
The polyQ expansion in the N-terminus of huntingtin protein confers a gain-of-function phenotype, and is associated with significant neurotoxicity (Tallaksen-Greene et al., 2003)
In Embodiment 74 of the invention, the compound of formula I, or a pharmaceutically acceptable salt thereof, is: 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (S)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(4-fluorophenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, 1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3-(5-(difluoromethoxy)pyridin-3-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N((R)-3-methyltetrahydrofuran-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N((S)-3-methyltetrahydrofuran-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N-(3,3-difluoro-1-methylcyclobutyl)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N((R)-3,3-difluoro-1-(hydroxymethyl)cyclopentyl)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N((S)-3,3-difluoro-1-(hydroxymethyl)cyclopentyl)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(3,5-difluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, 1-(5-chloropyrimidin-2-yl)-3-(3-(difluoromethoxy)phenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, ((R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-(3,5-difluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(3,3-difluorocyclobutyl)phenyl)-1-(4-fluorophenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N((S)-3-cyanotetrahydrofuran-3-yl)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N((R)-3-cyanotetrahydrofuran-3-yl)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, 3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N-((1R,2R)-2-morpholinocyclopentyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-(difluoromethoxy)-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-(tetrahydro-2H-pyran-4-yl)-N-(2-(6-(trifluoromethyl)pyridin-3-yl)propan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N((R)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-cyclopropoxyphenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-ethoxyphenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(3-(2,2,2-trifluoroethoxy)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(3-(1,1,2,2-tetrafluoroethoxy)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-cyclopropoxy-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-isopropoxypyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-chloro-2-ethoxypyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-(2,2-difluoroethoxy)-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-(difluoromethoxy)-5-fluoropyridin-4-yl)-1-isopropyl-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-(difluoromethyl)pyridin-3-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-isopropyl-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-(propan-2-yl-d 7 )-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-(propan-2-yl-d 7 )-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((R)-1,1-difluoropropan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((S)-1,1-difluoropropan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((R)-1,1-difluoropropan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((S)-1,1-difluoropropan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-(ethoxy-d 5 )-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N-(4-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-(propan-2-yl-d 7 )-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N-(4-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-((R)-1,1,1-trifluoropropan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-((S)-1,1,1-trifluoropropan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-ethoxy-2-fluorophenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(3-(trifluoromethoxy)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-cyclobutyl-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-((R)-1-cyclopropylethyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-((S)-1-cyclopropylethyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, ethyl 3-((R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamido)-3-methylpyrrolidine-1-carboxylate, (6R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(1-(isopropylcarbamoyl)-3-methylpyrrolidin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (6R)N-(1-(cyclopropanecarbonyl)-3-methylpyrrolidin-3-yl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-fluoro-5-isopropoxyphenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-cyclopropyl-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-chloro-5-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-cyclopropoxy-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-methylpyridin-3-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-ethoxy-2,3-difluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-chloro-5-(trifluoromethoxy)pyridin-3-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N-(3,3-difluoro-1-methylcyclobutyl)-3-(5-(difluoromethoxy)-2-methylpyridin-3-yl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(5-(1,1,2,2-tetrafluoroethoxy)pyridin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(5-(1,1,2,2-tetrafluoroethoxy)pyridin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-(1,1,2,2-tetrafluoroethoxy)pyridin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N-(4-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N-(4-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1R,2S)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1R,2R)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1S,2S)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1S,2R)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1-(methylsulfonyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-(cyclopropylsulfonyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, 3-(3-(difluoromethoxy)phenyl)-4,4-difluoro-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-4,4-difluoro-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (S)-3-(3-(difluoromethoxy)phenyl)-4,4-difluoro-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, 3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, 3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, 3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, (S)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, 3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, 3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, 3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N((R)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, N-(3,3-difluoro-1-methylcyclobutyl)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, (S)-3-(3-cyclopropylphenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide, (R)-3-(3-(1-fluorocyclopropyl)phenyl)-1-(4-fluorophenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(2-aminopropan-2-yl)phenyl)-1-(4-fluorophenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(6-(difluoromethoxy)pyrazin-2-yl)-1-(5-fluoropyridin-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-(5-fluoropyridin-2-yl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(1-methyl-1H-pyrazol-5-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(pyridin-3-ylmethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(isoxazol-4-ylmethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (6R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(1-isopropyl-2-oxopyrrolidin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N((S)-1-hydroxypropan-2-yl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(1-methoxy-2-methylpropan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-isopropyl-N((S)-1-((R)-2-methylmorpholino)propan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N-(3-ethyl-1,1-dioxidothietan-3-yl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N-(2-(1,1-dioxidothiomorpholino)ethyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(2-(N-methylsulfamoyl)ethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N((R)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(1-methylpiperidin-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-acetyl-3-(3-(difluoromethoxy)phenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-(cyclopropanecarbonyl)-3-(3-(difluoromethoxy)phenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-carbonyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-benzoyl-3-(3-(difluoromethoxy)phenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-benzyl-3-(3-(difluoromethoxy)phenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-N((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (6R)-1-(1-cyanoethyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (6R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1-(1-(thiazol-2-yl)ethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(3-(1-(trifluoromethyl)cyclopropyl)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(1-cyanocyclopropyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(2-(1,1-difluoroethyl)-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(2-methylbenzo[d]oxazol-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(cyanomethyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-(tert-butylcarbamoyl)pyridin-3-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(cyanomethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(1H-pyrazol-1-yl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(3-(methylsulfonyl)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(N-ethylsulfamoyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-ethyl-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(5-cyano-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(1,1-difluoroethyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)N-(3,3-difluoro-1-methylcyclobutyl)-3-(3-(1-hydroxycyclobutyl)phenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide, (R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide, (S)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide, (R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide, or (R)-3-(5-cyclopropyl-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide
