Heterocyclic kinase inhibitors

Abstract

This invention provides compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers, and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

What is claimed: 
     
         1 . A compound of Formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 U is CR 1  or N; 
 X is CR 2  or N; 
 Y is CR 3  or N; 
 Z is CR 4  or N; 
 R 1  is independently H or deuterium; 
 R 2  is H, deuterium, optionally substituted (C 1 -C 3 )alkyl, or CF 3 ; 
 R 3  is H, deuterium or optionally substituted (C 1 -C 3 )alkyl; 
 R 4  is H or deuterium; 
 R 5  is —R 501 -L-R 502  wherein
 R 501  is a bond, —O—, —OCH 2 —, or optionally substituted (C 1 -C 3 )alkylene, 
 L is —C(═O)—, —CH 2 N(H)C(═O)—, —N(H)C(═O)—, or N(H)S(O) 2 ; or 
 L is a bond and R 302  is —CN; or 
 L is -L 1 -L 2  wherein L 1  is attached to R 501  wherein
 L 1  is optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted saturated or partially saturated heterocyclyl, or optionally substituted saturated or partially saturated (C 3 -C 7 )cycloalkyl and L 2  is a bond, —CH 2 N(R a )—, —CH 2 N(R a )C(O)—, —N(R a )C(O)—, —N(R a )S(O) 2 — or —N(R a )—; or 
 L 1  is a saturated or partially saturated heterocyclyl containing one or more heteroatoms wherein at least one heteroatom is nitrogen and L 2  is a bond, C(O) or —S(O) 2 —; 
 
 R 502  is H, CF 3 , OH, optionally substituted (C 1 -C 6 )alkyl, optionally substituted alkenyl, optionally substituted alkynyl, CN, or optionally substituted (C 3 -C 6 )cycloalkenyl; 
 
 R 6  is optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 12 )cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, or optionally substituted heterocyclyl; or 
 R 6  is —R 601 —R 602  wherein R 601  is attached to the —N(H)— and
 R 601  is optionally substituted heteroaryl; 
 R 602  is N(R a ) 2 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 6 )cycloalkyl, or optionally substituted heterocyclyl; and 
 
 R a  is independently H or optionally substituted (C 1 -C 6 )alkyl; 
 provided the compound is not 2-(3-{8-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-imidazo[1,2-a]pyridine-6-yl}-phenyl)-N-(5,5,5-trifluoro-4-hydroxy-4-methyl-pent-2-ynyl)-acetamide. 
 
     
     
         2 . The compound according to  claim 1  wherein
 U is CR 1  or N; 
 X is CR 2  or N; 
 Y is CR 3  or N; 
 Z is CR 4  or N; 
 R 1  is independently H or deuterium; 
 R 2  is H, deuterium, optionally substituted (C 1 -C 3 )alkyl, or CF 3 ; 
 R 3  is H, deuterium or optionally substituted (C 1 -C 3 )alkyl; 
 R 4  is H or deuterium; 
 R 5  is —R 501 -L-R 502  wherein
 R 501  is a bond, —O—, —OCH 2 —, or optionally substituted (C 1 -C 3 )alkylene, 
 L is —C(═O)—, —CH 2 N(H)C(═O)—, —N(H)C(═O)—, or —N(H)S(O) 2 ; or 
 L is a bond and R 502  is —CN; or 
 L is -L 1 -L 2  wherein L 1  is attached to R 501  wherein
 L 1  is optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted saturated or partially saturated heterocyclyl, or optionally substituted saturated or partially saturated (C 3 -C 6 )cycloalkyl and L 2  is a bond, —CH 2 N(R a )—, —CH 2 N(R a )C(O)—, —N(R a )C(O)—, —N(R a )S(O) 2 — or —N(R a )—; or 
 L 1  is a saturated or partially saturated heterocyclyl containing one or more heteroatoms wherein at least one heteroatom is nitrogen and L 2  is a bond, C(O) or —S(O) 2 —; 
 
 R 502  is H, optionally substituted alkenyl, optionally substituted alkynyl, CN, or optionally substituted (C 3 -C 6 )cycloalkenyl; 
 
 R 6  is optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 12 )cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, or optionally substituted heterocyclyl; and 
 R a  is independently H or optionally substituted (C 1 -C 6 )alkyl. 
 
     
     
         3 . The compound of  claim 1  wherein
 L is —C(═O)—, —CH 2 N(H)C(═O)—, —N(H)C(═O)—, or —S(O) 2 ; and R 502  is H, —CH═CH 2  or —C≡CH; or 
 L is a bond and R 502  is —CN; or 
 L is -L 1 -L 2  wherein L 1  is attached to R 501  wherein
 L 1  is optionally substituted phenyl, optionally substituted heteroaryl or optionally substituted saturated or partially saturated (C 3 -C 6 )cycloalkyl and L 2  is —CH 2 N(R a )—, —CH 2 N(R a )C(O)—, —N(R a )C(O)—, —N(R a )S(O) 2 — or —N(R a )—; or 
 L 1  is optionally substituted heteroaryl, optionally substituted azepanyl, optionally substituted azetidinyl, optionally substituted morpholinyl, optionally substituted oxazepanyl, optionally substituted piperidinyl, optionally substituted pyrrolidinyl, optionally substituted tetrahydrofuranyl, or optionally substituted tetrahydropyranyl, and L 2  is a bond, C(O) or —S(O) 2 —. 
 
 
     
     
         4 . The compound of  claim 2  wherein R 6  is optionally substituted (C 1 -C 6 )alkyl, optionally substituted phenyl, optionally substituted bicycle[1.1.1]pentanyl, optionally substituted 1,2,4 oxadiazolyl, optionally substituted pyrazolyl, optionally substituted pyridazinyl, optionally substituted pyridinyl, 4,5-dihydro-1H-benzo[b]azepin-2(3H)-one, 3,4-dihydroquinolin-2(1H)-one, 2H-benzo[b][1,4]oxazin-3(4H)-one, or 6,7-dihydro-4H-pyrazolo [5,1-c][1,4]oxazinyl. 
     
     
         5 . The compound of  claim 3  wherein R 6  is optionally substituted with one or more substituents independently selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, optionally substituted imidazolidinone, or morpholinyl. 
     
     
         6 . The compound of  claim 4  wherein -L-R 502  forms —CN, —CH 2 N(H)C(═O)CH═CH 2 , —C(═O)CH═CH 2 , —N(H)C(═O)CH═CH 2 , —N(H)CN, or —S(O) 2 CH═CH 2 . 
     
     
         7 . The compound according to  claim 1  wherein the compound is
 N-(3-(8-((4-morpholinophenyl)amino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)benzyl)acrylamide; 
 N-(3-(8-(bicyclo[1.1.1]pentan-1-ylamino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)benzyl)acrylamide; 
 N-(3-(8-(bicyclo[1.1.1]pentan-1-ylamino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)phenyl)acrylamide; 
 1-(3-(8-((3,4-dimethoxyphenyl)amino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 8-((5-(1-acryloylpyrrolidin-3-yl)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 
 1-(3-(8-((4-morpholinopyridin-2-yl)amino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((5-methoxypyridazin-3-yl)amino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyridin-5-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 N-(2-(8-(bicyclo[1.1.1]pentan-1-ylamino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)phenyl)acrylamide; 
 1-((3R)-3-(8-((3,4-di methoxyphenyl)amino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-((3S)-3-(8-((3,4-dimethoxyphenyl)amino)-1,8a-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 8-((6-(1-acryloylpiperidin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 
 N-(3-(8-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)phenyl)acrylamide; 
 N-(3-(8-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzyl)acrylamide; 
 1-(3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 7-((6-(1-acryloylpyrrolidin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 
 6-((6-(1-acryloylpyrrolidin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-2H-benzo [b][1,4]oxazin-3(4H)-one; 
 8-((6-(1-acryloylpyrrolidin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 
 (S)-8-((6-(1-acryloylpyrrolidin-3-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-4,5-dihydro-1H-benzo [b]azepin-2(3H)-one; 
 (R)-8-((6-(1-acryloylpyrrolidin-3-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-4,5-dihydro-1H-benzo [b]azepin-2(3H)-one; 
 (S)—N-(3,4-dimethoxyphenyl)-6-(1-(vinylsulfonyl)pyrrolidin-3-yl)-[l 1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 1-(3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((6-morpholinopyridazin-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-(methylamino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((2-methoxyethyl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((5-morpholinopyridin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((1-methyl-1H-pyrazol-4-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((6-morpholinopyridin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 (S)-1-(3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 (R)-1-(3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((6-morpholinopyridin-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((6-morpholinopyridin-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((3-isopropyl-1,2,4-oxadiazol-5-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 N-((1R,3S)-3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)cyclohexyl)acrylamide; 
 N-((1S,3S)-3-(8-((1-methyl-1H-pyrazol-3-yl)methyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)cyclohexyl)acrylamide; 
 1-(3-(8-((3-methyl-1,2,4-oxadiazol-5-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 N-((1S,3S)-3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)cyclohexyl)cyanamide; 
 3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidine-1-carbonitrile; 
 3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrrolidine-1-carbonitrile; 
 1-(4-((6-(1-acryloylpyrrolidin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)phenyl)-3-methylimidazolidin-2-one; 
 3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidine-1-carbonitrile; 
 N-((1R,3S)-3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)cyclopentyl)acrylamide; 
 N-((1 S)-3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)cyclopentyl)acrylamide; 
 3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidine-1-carbonitrile; 
 (S)-1-(3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 (R)-1-(3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((1-methyl-1H-pyrazol-3-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 (S)-1-(3-(8-((1-methyl-1H-pyrazol-4-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 (R)-1-(3-(8-((1-methyl-1H-pyrazol-4-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; 
 (S)-1-(3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one; 
 1-(3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-1-yl)prop-2-en-1-one; or 
 (R)-1-(3-(8-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)piperidin-1-yl)prop-2-en-1-one. 
 
     
     
         8 . The compound according to  claim 1  wherein
 R 5  is —R 501 -L-R 502  wherein
 R 501  is a bond; 
 L is -L 1 -L 2  wherein L 1  is attached to R 501  wherein
 L 1  is optionally substituted saturated or partially saturated (C 3 -C 7 )cycloalkyl and L 2  is a bond-CH 2 N(R a )C(O)—, or —N(R a )C(O)—; and 
 R 502  is H, CF 3 , OH, optionally substituted (C 1 -C 6 )alkyl, optionally substituted alkenyl, optionally substituted alkynyl, CN, or optionally substituted (C 3 -C 6 )cycloalkenyl. 
 
 
 
     
     
         9 . A compound according to  claim 8  wherein
 R 6  is optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 12 )cycloalkyl, optionally substituted phenyl, optionally substituted pyrazolyl, optionally substituted 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, optionally substituted 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl; or 
 R 6  is —R 601 —R 602  wherein R 601  is attached to the —N(H)— and 
 R 601  is optionally substituted pyrazolyl, or optionally substituted pyridinyl; 
 R 602  is N(R a ) 2 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted azetidinyl, optionally substituted morpholinyl, optionally substituted piperidinyl, or optionally substituted tetrahydropyranyl. 
 
     
     
         10 . The compound according to  claim 9  wherein R 1  is H. 
     
     
         11 . The compound according to  claim 10  wherein X is N or CR 2  wherein R 2  is H, optionally substituted (C 1 -C 3 )alkyl, or CF 3 . 
     
     
         12 . The compound according to  claim 11  wherein R 3  is H, deuterium or optionally substituted (C 1 -C 3 )alkyl. 
     
     
         13 . The compound according to  claim 12  wherein U is CH. 
     
     
         14 . The compound according to  claim 13  wherein X is N. 
     
     
         15 . The compound according to  claim 1  wherein the compound is
 4-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)-2-methylbutan-2-ol; 
 6-cyclohexyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 6-cyclohexyl-N-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 6-cyclohexyl-N-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 (1R,4R)-4-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol; 
 (1S,4S)-4-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol; 
 6-cyclohexyl-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 (6-cyclohexyl-N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 6-cyclopentyl-N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 6-cyclohexyl-N-(1-isopropyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 6-(4,4-dimethylcyclohexyl)-N-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 N-(1-methyl-1H-pyrazol-4-yl)-6-((1R,4R)-4-methylcyclohexyl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 N-(1-methyl-1H-pyrazol-4-yl)-6-((1S,4S)-4-methylcyclohexyl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 N-(1-methyl-1H-pyrazol-4-yl)-6-((1r,4r)-4-(trifluoromethyl)cyclohexyl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 N-(6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-amine; 
 6-cyclohexyl-N-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-amine; 
 6-cyclopentyl-N-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 6-cyclopentyl-N-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-amine; 
 1-(4-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethanone; 
 4-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)-N-methylpiperidine-1-carboxamide; 
 (1S,3S)-3-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol; 
 (1R,3R)-3-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol; 
 (1R,3S)-3-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol; 
 (1S,3R)-3-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol; 
 (1R,3R)-3-(8-((1-methyl-1H-pyrazol-4-yl)amino)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)cyclohexanol; 
 1-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol; 
 N-(6-cyclopentyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-amine; 
 1-(6-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)amino)pyridin-3-yl)piperidin-4-ol; 
 6-cyclohexyl-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 (1S,4S)-ethyl 4-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarboxylate; 
 6-cyclopentyl-N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 6-cyclohexyl-N-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine; 
 cis-4-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarboxylic acid; or 
 3-(4-((6-cyclohexyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)propan-1-ol. 
 
     
     
         16 . A method of treating a disease comprising administering a therapeutically effective amount of a compound of  claim 1  to a patient in need thereof. 
     
     
         17 . The method according to  claim 16 , wherein the disease is rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, Crohn's disease, inflammatory bowel disease, irritable bowel syndrome, ulcerative colitis, psoriatic arthritis, psoriasis, ankylosing spondylitis, interstitial cystitis, asthma, systemic lupus erythematosus, lupus nephritis, B cell chronic lymphocytic lymphoma, multiple sclerosis, chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, B-cell non-Hodgkin's lymphoma, activated B-cell like diffuse large B-cell lymphoma, multiple myeloma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia or Lymphoblastic lymphoma. 
     
     
         18 . A kit comprising a packaged product comprising components with which to administer a compound of  claim 1  for treatment of an autoimmune disorder. 
     
     
         19 . The kit according to  claim 18 , wherein the packaged product comprises a compound of  claim 1  and instructions for use. 
     
     
         20 . A pharmaceutical composition comprising a compound according to  claim 1  and one or more pharmaceutically acceptable excipients.