N-(2-cyano heterocyclyl) pyrazolo pyridones as janus kinase inhibitors

A compound, or a pharmaceutically acceptable salt, or a stereoisomer thereof selected from:

• 3-(3-((4-(methyl sulfonyl)phenyl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(4-oxo-3-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-((2-methyl-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-5-yl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-((2-(tert-butyl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-5-yl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 4-((1-(4-cyanotetrahydro-2H-pyran-3-yl)-4-oxo-4, 5-dihydro-H-pyrazolo[4,3-c]pyridin-3-yl)amino)-N,N-dimethylbenzenesulfonamide;
• 3-(3-((1,1-dioxido-2-(2,2,2-trifluoroethyl)-2,3-dihydrobenzo[d]isothiazol-5-yl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-((4-(1-amino-2,2,2-trifluoroethyl)phenyl)amino)-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• N-(tert-butyl)-4-((1-(4-cyanotetrahydro-2H-pyran-3-yl)-4-oxo-4, 5-dihydro 1H-pyrazolo[4,3-c]pyridin-3-yl)amino)benzenesulfonamide;
• 3-(3-((4-(isopropylsulfonyl)phenyl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• N-(tert-butyl)-4-((1-(4-cyanotetrahydro-2H-pyran-3-yl)-4-oxo-4, 5-dihydro 1H-pyrazolo[4,3-c]pyridin-3-yl)amino)-N-methylbenzenesulfonamide;
• 3-(3-((4-(tert-butyl sulfonyl)phenyl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-{[2-(2-methylpropyl)-2,3-dihydro-1H-isoindol-5-yl]amino}-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-{[2-(1-methylethyl)-2,3-dihydro-1H-isoindol-5-yl]amino}-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• methyl 5-({1-[4-cyanotetrahydro-2H-pyran-3-yl]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl}amino)-2-hydroxybenzenecarboximidoate;
• 3-{3-[(4-fluoro-3-methoxyphenyl)amino]-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[1-(dimethylamino)-2,2,2-trifluoroethyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-{[4-(5,5-dimethyl-3-oxo-2-oxabicyclo[2.2.2]oct-1-yl)phenyl]amino}-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-{[4-(tert-butylsulfonyl)phenyl]amino}-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)oxepane-4-carbonitrile;
• 3-(3-{[4-(tert-butylsulfonyl)phenyl]amino}-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)oxepane-4-carbonitrile;
• 5-(3-{[4-(tert-butylsulfonyl)phenyl]amino}-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)oxepane-4-carbonitrile;
• 5-(3-{[4-(tert-butyl sulfonyl)phenyl]amino}-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)oxepane-4-carbonitrile;
• 3-{3-[(2-fluoropyridin-4-yl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-cyanophenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-cyano-3-fluorophenyl)amino]-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-(4-oxo-3-((4-((S or R)-1,1,1-trifluoro-2-methoxypropan-2-yl)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-((2,3-dimethyl-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-5-yl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-((4-(4,4-difluoropiperidine-1-carbonyl)-3-methylphenyl)amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-[4-oxo-3-({4-[2,2,2-trifluoro-1-(4-methylpiperazin-1-yl)ethyl]phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-[4-oxo-3-({4-[2,2,2-trifluoro-1-piperazin-1-ylethyl]phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• tert-butyl N-{1-[4-({1-[4-cyanotetrahydro-2H-pyran-3-yl]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl}amino)phenyl]-2,2,2-trifluoroethyl}glycinate;
• 3-[4-oxo-3-({4-[2,2,2-trifluoro-1-pyrrolidin-1-ylethyl]phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-[4-oxo-3-({4-[1-(2H-1,2,3-triazol-2-yl)ethyl]phenyl}amino)-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[{[(2,2-dimethylcyclopropyl)amino]-2,2,2-trifluoroethyl}phenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[1-(tert-butylamino)-2,2,2-trifluoroethyl]phenyl)}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-{4-oxo-3-[(4-{2,2,2-trifluoro-1-[(1-methylethyl)amino]ethyl}phenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[1-(ethylamino)-2,2,2-trifluoroethyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[1-azetidin-1-yl-2,2,2-trifluoroethyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[1-(dimethylamino)-2,2,2-trifluoroethyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-{[4-(1-amino-1-methylethyl)phenyl]amino}-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-{1-methyl-1-[(1-methylethyl)amino]ethyl}phenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-{[1,1-dioxido-2-(2,2,2-trifluoroethyl)-2,3-dihydro-1,2-benzisothiazol-5-yl]amino}-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• N-tert-butyl-4-({1-[4-cyanotetrahydro-2H-pyran-3-yl]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl}amino)-N-methylbenzenesulfonamide;
• tert-butyl [5-({1-[4-cyanotetrahydro-2H-pyran-3-yl]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl}amino)-1,1-dioxido-1,2-benzisothiazol-2(3H)-yl]acetate;
• 3-[3-({4-[(1,1-dimethylpropyl)sulfonyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-[4-oxo-3-({4-[(1,1,2-trimethylpropyl)sulfonyl]phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 5-({1-[4-cyanotetrahydro-2H-pyran-3-yl]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl}amino)-N,N-dimethylpyridine-2-sulfonamide;
• 3-{3-[(3,4-dimethylphenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-{[4-(azetidin-1-ylsulfonyl)phenyl]amino}-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[(3-methylazetidin-1-yl)sulfonyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[(2,2-dimethylmorpholin-4-yl)sulfonyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[(2,2-dimethylpyrrolidin-1-yl)sulfonyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-{[2,6-dimethylmorpholin-4-yl]sulfonyl}phenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-{[2-methylmorpholin-4-yl]sulfonyl}phenyl)amino]-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-{[2,6-dimethylmorpholin-4-yl]sulfonyl}phenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-{[2-methylazetidin-1-yl]sulfonyl}phenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• N-(tert-butyl)-4-((1-(4-cyanotetrahydro-2H-pyran-3-yl)-4-oxo-4, 5-dihydro 1H-pyrazolo[4,3-c]pyridin-3-yl)amino)-N-ethylbenzenesulfonamide;
• 3-[3-({4-[1-(cyclopropylamino)-2,2,2-trifluoroethyl]phenyl}amino)-4-oxo-4,5 dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(4-{1-[(2,2-dimethylpropyl)amino]-2,2,2-trifluoroethyl}phenyl)amino]-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[1-(cyclopentylamino)-2,2,2-trifluoroethyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-{4-oxo-3-[(4-{2,2,2-trifluoro-1-[2-methylpyrrolidin-1-yl]ethyl}phenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-{4-oxo-3-[(4-{2,2,2-trifluoro-1-[(2-methylpropyl)amino]ethyl}phenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({4-[1-(cyclobutylamino)-2,2,2-trifluoroethyl]phenyl}amino)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-(4-oxo-3-((4-(2,2,2-trifluoro-1-hydroxy-1-(pyridin-4-yl)ethyl)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(4-oxo-3-((4-(2,2,2-trifluoro-1-hydroxy-1-(pyridin-2-yl)ethyl)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(4-oxo-3-((4-((3-(trifluoromethyl)pyrrolidin-3-yl)phenyl)amino)-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-[3-({3-methyl-3-[(1-methylethyl)amino]-2-oxo-2,3-dihydro-1H-indol-6-yl}amino)-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(2-methyl-1,3-benzothiazol-6-yl)amino]-4-oxo-4,5-dihydro-H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-{3-[(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-6-yl)amino]-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl}tetrahydro-2H-pyran-4-carbonitrile;
• 3-[4-oxo-3-({4-[2,2,2-trifluoro-1-hydroxy-1-methylethyl]phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl]tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-((4-chloro-3-(methylsulfonyl)phenyl)amino)-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile;
• 3-(3-((4-fluoro-3-(methyl sulfinyl)phenyl)amino)-4-oxo-4, 5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile, and
• 3-(3-{[4-chloro-3-(methylsulfinyl)phenyl]amino}-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-1-yl)tetrahydro-2H-pyran-4-carbonitrile.