	US 11,673,886 B2
	5-membered and bicyclic heterocyclic amides as inhibitors of ROCK
Peter W. Glunz, Yardley, PA (US); Vladimir Ladziata, Ewing, NJ (US); Indawati De Lucca, Pennington, NJ (US); George O. Tora, Langhorne, PA (US); Tarun Kumar Maishal, Bangalore (IN); Raghuram Tangirala, Bengaluru (IN); and Kamalraj Thiyagarajan, Vellore (IN)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
Filed on Jun. 17, 2021, as Appl. No. 17/349,980.
Application 17/349,980 is a continuation of application No. 16/629,717, granted, now 11,078,197, previously published as PCT/US2018/041573, filed on Jul. 11, 2018.
Claims priority of provisional application 62/531,563, filed on Jul. 12, 2017.
Prior Publication US 2022/0356179 A1, Nov. 10, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 417/12 (2006.01); C07D 401/14 (2006.01); C07D 403/12 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 495/04 (2006.01); C07D 519/00 (2006.01); C07D 491/052 (2006.01)

CPC C07D 417/12 (2013.01) [C07D 401/14 (2013.01); C07D 403/12 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 491/052 (2013.01); C07D 495/04 (2013.01); C07D 519/00 (2013.01)]

5 Claims

1. A compound selected from:

4-(((aR)-6-(1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-carboxamido)spiro[3.3]heptan-2-yl)oxy)-2-methylthiazole-5-carboxamide;

N-((aR)-6-((2-carbamoyl-benzo[b]thiophen-3-yl)oxy)spiro[3.3]heptan-2-yl)-7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carboxamide;

2-cyclopropyl-4-(((aR)-6-(6-(2-oxopyridin-1(2H)-yl)-3-(trifluoromethyl)imidazo[1,5-a]pyridine-1-carboxamido)spiro[3.3]heptan-2-yl)oxy)thiazole-5-carboxamide;

N-((aR)-6-((4-carbamoyl-1-methyl-1H-pyrazol-3-yl)oxy)spiro[3.3]heptan-2-yl)-6-(3,3,3-trifluoropropoxy)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-((aR)-6-((4-carbamoyl-1-(cyclopropylmethyl)-1H-pyrazol-3-yl)oxy)spiro[3.3]heptan-2-yl)-7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-((aR)-6-((3-carbamoyl-pyrazolo[1,5-a]pyridin-2-yl)oxy)spiro[3.3]heptan-2-yl)-7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carboxamide;

2-(((aR)-6-(7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carboxamido)spiro[3.3]heptan-2-yl)oxy)-1,8-naphthyridine-3-carboxamide;

2-(((aR)-6-(7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carboxamido)spiro[3.3]heptan-2-yl)oxy)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carboxamide;

5-((6-(4-(trifluoromethyl)cyclohexane-1-carboxamido)spiro[3.3]heptan-2-yl)oxy)thieno[3,2-b]pyridine-6-carboxamide;

1-cyclopropyl-3-(((aR)-6-(4-isobutyl-2,5-dioxoimidazolidin-1-yl)spiro[3.3]heptan-2-yl)oxy)-1H-pyrazole-4-carboxamide;

2-cyclopropyl-4-(((aR)-6-(6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-carboxamido)spiro[3.3]heptan-2-yl)oxy)thiazole-5-carboxamide;

6-(2-hydroxy-2-methylpropoxy)-N-[(aR)-6-({3-carbamoyl-5H,7H,8H-pyrano[4,3-b]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]pyrazolo[1,5-a]pyridine-3-carboxamide;

2-(((aR)-6-(4-benzyl-2,6-dioxopiperazin-1-yl)spiro[3.3]heptan-2-yl)oxy)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carboxamide;

3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-methyl-1H-pyrazole-4-carboxamide;

3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-phenyl-1H-pyrazole-4-carboxamide;

1-phenyl-3-({(aR)-6-[6-(3,3,3-trifluoropropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

4-({(aR)-6-[6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-2-phenyl-1,3-thiazole-5-carboxamide;

4-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-2-phenyl-1,3-thiazole-5-carboxamide;

3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-ethyl-1H-pyrazole-4-carboxamide;

3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-[(piperidin-4-yl)methyl]-1H-pyrazole-4-carboxamide;

4-({(aR)-6-[6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-2-methyl-1,3-thiazole-5-carboxamide;

4-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-2-methyl-1,3-thiazole-5-carboxamide;

3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide;

5-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide;

N-{(aR)-6-[(5-carbamoyl-2-methyl-1,3-thiazol-4-yl)oxy]spiro[3.3]heptan-2-yl}-1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-1H-indazole-3-carboxamide;

5-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

1-(3-aminopropyl)-3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

1-(3-aminopropyl)-5-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

1-(2-aminoethyl)-3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-(difluoromethyl)-1H-pyrazole-4-carboxamide;

1-(2-cyanophenyl)-3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

1-methyl-3-({(aR)-6-[6-(morpholin-4-yl)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

1-methyl-3-{[(aR)-6-(6-{2-oxa-6-azaspiro[3.3]heptan-6-yl}pyrazolo[1,5-a]pyridine-3-amido)spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

4-[((aR)-6-{6-[3-(chloromethyl)-3-(hydroxymethyl)azetidin-1-yl]pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl)oxy]-2-methyl-1,3-thiazole-5-carboxamide;

1-methyl-3-({(aR)-6-[6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

N-{(aR)-6-[(4-carbamoyl-1-methyl-1H-pyrazol-3-yl)oxy]spiro[3.3]heptan-2-yl}-1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-1H-indazole-3-carboxamide;

3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1,5-dimethyl-1H-pyrazole-4-carboxamide;

3-({(aR)-6-[1-(4-cyanophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl}oxy)-1-phenyl-1H-pyrazole-4-carboxamide;

5-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1-(difluoromethyl)-1H-pyrazole-4-carboxamide;

1-phenyl-3-{[(aR)-6-[6-(3,3,3-trifluoropropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-phenyl-3-{[(aR)-6-{3-cyano-5-[1-(difluoromethyl)-1H-pyrazol-4-yl]benzamido}spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(aR)-6-[(4-carbamoyl-1-phenyl-1H-pyrazol-3-yl)oxy]spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

2-methyl-4-{[(aR)-6-[1-(4-cyanophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[1-(4-cyanophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

1-(4-cyanophenyl)-5-methyl-N-[(aR)-6-[(4-carbamoyl-1-methyl-1H-pyrazol-3-yl)oxy]spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-(4-chlorophenyl)-5-methyl-N-[(aR)-6-[(4-carbamoyl-1-methyl-1H-pyrazol-3-yl)oxy]spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-(6-methoxypyridin-3-yl)-5-methyl-N-[(aR)-6-[(4-carbamoyl-1-methyl-1H-pyrazol-3-yl)oxy]spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-phenyl-3-f{[(aR)-6-[1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-{[(aR)-6-[1-(6-methoxypyridin-3-yl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-{[(aR)-6-[1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-(difluoromethyl)-3-{[(aR)-6-{6-[3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propoxy]pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-(difluoromethyl)-3-{[(aR)-6-[6-(2,2,2-trifluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-(4-cyanophenyl)-5-methyl-N-[(aR)-6-{[4-carbamoyl-1-(difluoromethyl)-1H-pyrazol-3-yl]oxy}spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-(4-chlorophenyl)-5-methyl-N-[(aR)-6-{[4-carbamoyl-1-(difluoromethyl)-1H-pyrazol-3-yl]oxy}spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-f{[(aR)-6-[6-(2,2,2-trifluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-f{[(aR)-6-[6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-{[(aR)-6-[3-(trifluoromethyl)imidazo[1,5-a]pyridine-1-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-{[(aR)-6-[6-(6-fluoropyridin-3-yl)-3-(trifluoromethyl)imidazo[1,5-a]pyridine-1-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-{[(aR)-6-[6-bromo-3-(trifluoromethyl)imidazo[1,5-a]pyridine-1-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

2-cyclopropyl-4-{[(aR)-6-{6-[3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propoxy]pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[6-(2,2,2-trifluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[6-(6-fluoropyridin-3-yl)-3-(trifluoromethyl)imidazo[1,5-a]pyridine-1-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[3-(trifluoromethyl)imidazo[1,5-a]pyridine-1-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

1-cyclopropyl-3-{[(aR)-6-(5-methyl-1-phenyl-1H-pyrazole-4-amido)spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-{[(aR)-6-[1-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[1-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-(5-methyl-1-phenyl-1H-pyrazole-4-amido)spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

1-cyclopropyl-3-({(aR)-6-[7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1H-pyrazole-4-carboxamide;

2-methyl-4-{[(aR)-6-[6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-(((aR)6-(7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carboxamido)spiro[3.3]heptan-2-yl)oxy)quinoline-3-carboxamide;

N-[6-({5-carbamoyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-2-(pyridin-4-yl)-1,3-thiazole-4-carboxamide;

6-({6-[6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;

1,3-dimethyl-6-[(6-{pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl)oxy]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;

5-[(6-{pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl)oxy]thieno[3,2-b]pyridine-6-carboxamide;

5-({6-[6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl}oxy)thieno[3,2-b]pyridine-6-carboxamide;

5-{[6-(4,4-difluorocyclohexaneamido)spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

N-[6-({6-carbamoylthieno[3,2-b]pyridin-5-yl}oxy)spiro[3.3]heptan-2-yl]-1-[(4-chlorophenyl)methyl]-5-oxopyrrolidine-3-carboxamide;

5-{[6-(3-cyanobenzamido)spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

2-[(6-{pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl)oxy]-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

N-[6-({3-carbamoyl-5H,7H,8H-pyrano[4,3-b]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carboxamide;

5-{[(aR)-6-(3-cyanobenzamido)spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

6-(2-hydroxy-2-methylpropoxy)-N-[(aR)-6-({6-carbamoylthieno[3,2-b]pyridin-5-yl}oxy)spiro[3.3]heptan-2-yl]pyrazolo[1,5-a]pyridine-3-carboxamide;

2-{[(aR)-6-(3-cyanobenzamido)spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

5-{[(aR)-6-(4-benzyl-2,6-dioxopiperazin-1-yl)spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

2-{[(aR)-6-(3-cyano-4-fluorobenzamido)spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

2-{[(aR)-6-[3-(cyanomethyl)benzamido]spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

2-{[(aR)-6-(5-cyano-2-fluorobenzamido)spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

2-{[(aR)-6-(3-cyano-4-methoxybenzamido)spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

N-[(aR)-6-({3-carbamoyl-5H,7H,8H-pyrano[4,3-b]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-5-carboxamide;

2-{[(aR)-6-(4-bromo-3-cyanobenzamido)spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

2-{[(aR)-6-(4-cyano-3-fluorobenzamido)spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

2,3-dimethyl-5-{[(aR)-6-[6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

2,3-dimethyl-5-{[(aR)-6-(3-cyanobenzamido)spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

6-fluoro-N-[(aR)-6-({6-carbamoyl-2,3-dimethylthieno[3,2-b]pyridin-5-yl}oxy)spiro[3.3]heptan-2-yl]quinoline-3-carboxamide;

3-methyl-5-f{[(aR)-6-[6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

3-methyl-5-{[(aR)-6-(3-cyanobenzamido)spiro[3.3]heptan-2-yl]oxy}thieno[3,2-b]pyridine-6-carboxamide;

6-fluoro-N-[(aR)-6-({6-carbamoyl-3-methylthieno[3,2-b]pyridin-5-yl}oxy)spiro[3.3]heptan-2-yl]quinoline-3-carboxamide;

6-fluoro-N-[(aR)-6-({3-carbamoyl-5H,7H,8H-pyrano[4,3-b]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]quinoline-3-carboxamide;

1-methyl-6-{[(aR)-6-[6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;

1-methyl-6-{[(aR)-6-(3-cyanobenzamido)spiro[3.3]heptan-2-yl]oxy}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;

6-fluoro-N-[(aR)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]quinoline-3-carboxamide;

1-cyclopropyl-3-{[(aR)-6-(4-benzyl-2,5-dioxoimidazolidin-1-yl)spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

1-cyclopropyl-3-f{[(aR)-6-[4-(2-methylpropyl)-2,5-dioxoimidazolidin-1-yl]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazole-4-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-{2,5-dioxo-4-[(pyridin-3-yl)methyl]imidazolidin-1-yl}spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-(4-ethyl-2,5-dioxoimidazolidin-1-yl)spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-{4-[(1R)-1-hydroxyethyl]-2,5-dioxoimidazolidin-1-yl}spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-cyclopropyl-4-{[(aR)-6-[4-(2-methylpropyl)-2,5-dioxoimidazolidin-1-yl]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

4-(((2S,4s,6S)-6-(1-(4-cyanophenyl)-5-methyl-1H-pyrazole-4-carboxamido)spiro[3.3]heptan-2-yl)oxy)-2-methoxythiazole-5-carboxamide;

2-(((2S,4s,6S)-6-(4-isobutyl-2,5-dioxoimidazolidin-1-yl)spiro[3.3]heptan-2-yl)oxy)pyrazolo[1,5-a]pyridine-3-carboxamide;

1-methyl-6-(((2S,4s,6S)-6-(5-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxamido)spiro[3.3]heptan-2-yl)oxy)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;

2-methoxy-4-{[(4s)-6-[1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-methoxy-4-{[(4s)-6-{5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-amido}spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-methoxy-4-{[(4s)-6-[6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-methoxy-4-{[(4s)-6-{6-[3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propoxy]pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

2-methoxy-4-{[(4s)-6-[6-(2,2,2-trifluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-1,3-thiazole-5-carboxamide;

1-(4-cyanophenyl)-5-methyl-N-[(4s)-6-({3-carbamoylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-(4-chlorophenyl)-5-methyl-N-[(4s)-6-({3-carbamoylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

5-methyl-N-[(4s)-6-({3-carbamoylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

2-{[(4s)-6-[6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}pyrazolo[1,5-a]pyridine-3-carboxamide;

2-{[(4s)-6-{6-[3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propoxy]pyrazolo[1,5-a]pyridine-3-amido}spiro[3.3]heptan-2-yl]oxy}pyrazolo[1,5-a]pyridine-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-6-methoxypyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

6-methoxy-2-{[(4s)-6-[6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}pyrazolo[1,5-a]pyridine-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-6-methylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

6-fluoro-2-{[(4s)-6-[6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}pyrazolo[1,5-a]pyridine-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-6-fluoropyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(4-cyanophenyl)-5-methyl-N-[(4s)-6-({3-carbamoyl-6-fluoropyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-{[3-carbamoyl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl]oxy}spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

2-{[(4s)-6-[6-(2,2-difluoroethoxy)pyrazolo[1,5-a]pyridine-3-amido]spiro[3.3]heptan-2-yl]oxy}-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-5-methylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-7-methylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-7-phenylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-{[3-carbamoyl-6-(6-fluoropyridin-3-yl)pyrazolo[1,5-a]pyridin-2-yl]oxy}spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-{[3-carbamoyl-5-(6-fluoropyridin-3-yl)pyrazolo[1,5-a]pyridin-2-yl]oxy}spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-5-phenylpyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(difluoromethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({3-carbamoyl-7-methoxypyrazolo[1,5-a]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

2-{[(4s)-6-[2,5-dioxo-4-(3,3,3-trifluoro-2-methylpropyl)imidazolidin-1-yl]spiro[3.3]heptan-2-yl]oxy}pyrazolo[1,5-a]pyridine-3-carboxamide;

5-[(2-methylpropyl)amino]-N-[(4s)-6-({3-carbamoyl-5H,7H,8H-pyrano[4,3-b]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1,3,4-thiadiazole-2-carboxamide;

2-{[(4s)-6-[3-(trifluoromethoxy)benzamido]spiro[3.3]heptan-2-yl]oxy}-5H,7H,8H-pyrano[4,3-b]pyridine-3-carboxamide;

2-[(2-hydroxy-2-methylpropyl)amino]-4-methyl-N-[(4s)-6-({3-carbamoyl-5H,7H,8H-pyrano[4,3-b]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1,3-thiazole-5-carboxamide;

4-methyl-2-[(2-methylpropyl)amino]-N-[(4s)-6-({3-carbamoyl-5H,7H,8H-pyrano[4,3-b]pyridin-2-yl}oxy)spiro[3.3]heptan-2-yl]-1,3-thiazole-5-carboxamide;

7-cyclopropyl-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]pyrazolo[1,5-a]pyridine-3-carboxamide;

6-(hydroxymethyl)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]pyridine-2-carboxamide;

N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazole-2-carboxamide;

1-(4-methanesulfonylphenyl)-5-methyl-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

5-(2,4-difluorophenyl)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1,3,4-thiadiazole-2-carboxamide;

1-(4-cyanophenyl)-5-methyl-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

5-methyl-1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-(difluoromethyl)-5-(4-methanesulfonylphenyl)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-3-carboxamide;

5-(4-cyanophenyl)-1-(difluoromethyl)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-3-carboxamide;

5-(3-methanesulfonylphenyl)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1,3,4-thiadiazole-2-carboxamide;

1-methyl-6-{[(4s)-6-[1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridine-5-amido]spiro[3.3]heptan-2-yl]oxy}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;

1-{4-[1-(2,2-difluoroethyl)-1H-pyrazol-4-yl]phenyl}-5-methyl-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide;

1-(2,2-difluoroethyl)-6-(2-hydroxy-2-methylpropoxy)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(2,2-difluoroethyl)-6-(2-fluoro-2-methylpropoxy)-N-[(4s)-6-({5-carbamoyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl}oxy)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide;

1-(2,4-difluorophenyl)-5-methyl-N-[(4s)-6-({6-carbamoyl-2,3-dimethylthieno[3,2-b]pyridin-5-yl}oxy)spiro[3.3]heptan-2-yl]-1H-pyrazole-4-carboxamide; and

5-[(2-methylpropyl)amino]-N-[(4s)-6-({6-carbamoyl-2,3-dimethylthieno[3,2-b]pyridin-5-yl}oxy)spiro[3.3]heptan-2-yl]-1,3,4-thiadiazole-2-carboxamide;

or a stereoisomer, an enantiomer, a diastereoisomer, a tautomer, or a pharmaceutically-acceptable salt thereof.