The present disclosure is directed to novel compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variables are as defined herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Crohn's disease, psoriasis and asthma.
1. A compound of Formula (I)
a pharmaceutically acceptable salt or stereoisomer thereof wherein
R 1 is —W—X—Y wherein W is directly attached to the nitrogen of the pyrazolyl ring;
W is phenylene, optionally substituted (C 1 -C 6 )alkylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene, (C 3 -C 6 )cycloalkylene, optionally substituted heterocyclylene or optionally substituted heteroarylene;
X is a bond, phenylene, optionally substituted (C 3 -C 6 )cycloalkylene, optionally substituted piperidinyl or optionally substituted heteroarylene;
Y is deuterium, —C(O)R a , —S(O) 2 N(R a ) 2 , —N(R a )S(O) 2 , —OR a , —N(R a )S(O) 2 R a , —C(O)N(R a ) 2 , —N(R a )C(O)R a , —N(R a ) 2 , S(O) 2 R a , —CH 3 , —CH 2 NH 2 , -optionally substituted (C 1 -C 6 )alkylene, —N(R a )C(O)O—R a , or optionally substituted (C 1 -C 6 )alkyl, provided that when W and X are both bonds then Y is not oxo, —N(R a )S(O) 2 R a , —N(R a )C(O)R a or —N(R a ) 2 ; or
Y is A-D wherein A is connected to X wherein
A is a bond, C(O), C(O)R b , R b C(O), S(O) 2 , optionally substituted (C 1 -C 6 )alkylene, N(R a )S(O) 2 R b , R b S(O) 2 N(R a ), N(R a )C(O), C(O)N(R a ), N(R a )S(O) 2 , S(O) 2 N(R a ), O, OR b , R b O, N(R a )R b , R b N(R a ), R b N(R a )C(O), C(O)N(R a )R b , R b N(R a )S(O) 2 , S(O) 2 N(R a )R b , N(R a )C(O)R b , R b C(O)N(R a ), R b N(R a ), S(O) 2 R b , R b S(O) 2 , and N(R a ); and
D is —CN, —C(O)N(R a ) 2 or N(R a ) 2 ; or
D is —O-optionally substituted (C 1 -C 6 )alkyl, optionally substituted aryl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted heterocyclyl or optionally substituted heteroaryl;
wherein D may be optionally substituted by one or more CN, halogen, —OH, —C(O)R a , —R a , —C(O)N(R a ) 2 , —O—R a , —N(R a )S(O) 2 R a , —S—R a , —S(O)—R a , —S(O) 2 —R a or —S(O) 2 N(R a ) 2 ;
provided that R 1 is not biphenyl, optionally substituted indanyl, optionally substituted indenyl, optionally substituted indolyl or optionally substituted tetrahydrofuranyl; or
R 1 is
wherein R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are independently H, CN, OH, optionally substituted (C 1 -C 6 )alkyl, —O-optionally substituted (C 1 -C 6 )alkyl or optionally substituted (C 3 -C 10 )cycloalkyl;
R 17 and R 18 are independently H, —S(O) 2 -optionally substituted (C 3 -C 10 )cycloalkyl, —S(O) 2 -optionally substituted aryl, —S(O) 2 -optionally substituted (C 1 -C 6 )alkyl, —S(O) 2 , —S(O) 2 -optionally substituted heterocyclyl, —S(O) 2 -optionally substituted heteroaryl, —C(O)-optionally substituted (C 3 -C 10 )cycloalkyl, —C(O)-optionally substituted aryl, —C(O)-optionally substituted (C 1 -C 6 )alkyl, —C(O)-optionally substituted heterocyclyl- or —C(O)-optionally substituted heteroaryl; or
R 17 and R 18 form a heterocyclic ring together with the nitrogen to which they are attached;
or
R 2 is H;
R 3 is H;
R 4 is H;
R 5 is -G-J wherein G is connected to the nitrogen atom and wherein
G is a bond, pyrazole or phenylene;
wherein the phenylene is optionally substituted with CH 3 ; and
J is H, optionally substituted (C 1 -C 3 )alkyl, —OR a , —C(O)R a , —S(O) 2 —R b , —S(O) 2 —N(R a ) 2 , optionally substituted thiomorpholinyl or optionally substituted piperazinyl;
wherein the piperazinyl is optionally substituted with CH 3 and provided that J is not triazolyl; or
R 4 and R 5 fuse to form a (C 2 -C 4 )heterocyclic ring which can be optionally substituted;
R a is independently H, deuterium, optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; and
R b is independently optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
and
provided that the compound is not
1-isopropyl-4-methyl-N-(5-(piperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
tert-butyl 4-(6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazolo[3,4-d]pyrimidine-1-yl)cyclohexyl carbamate;
1-cyclopentyl-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-d]pyrimdin-6-amine;
1-cyclohexyl-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine;
1-cyclohexyl-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine; or
tert-butyl 4-((1-cyclohexyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)benzoate.
2. The compound according to claim 1 wherein R 4 is H.
3. The compound of claim 2 wherein
R 1 is —W—X—Y wherein W is directly attached to the nitrogen of the pyrazolyl ring;
W is optionally substituted (C 1 -C 6 )alkylene, phenylene, (C 3 -C 6 )cycloalkylene, optionally substituted heterocyclylene or optionally substituted heteroarylene;
X is a bond, phenylene, optionally substituted (C 3 -C 6 )cycloalkylene, optionally substituted piperidinyl or optionally substituted pyridinyl;
Y is —C(O)R a , —S(O) 2 N(R a ) 2 , —N(R a )S(O) 2 , —OR a , N(R a )S(O) 2 R a , —C(O)N(R a ) 2 , —N(R a )C(O)R a , N(R a ) 2 , S(O) 2 R a , CH 3 or CH 2 NH 2 , provided that when W and X are both bonds that Y is not oxo, —N(R a )S(O) 2 , —N(R a )S(O) 2 R a , N(R a )C(O)R a or N(R a ) 2 ; or
Y is A-D wherein A is connected to X wherein
A is a bond, C(O), C(O)R b , R b C(O), S(O) 2 , optionally substituted (C 1 -C 6 )alkylene, N(R a )S(O) 2 R b , N(R a )C(O), C(O)N(R a ), N(R a )S(O) 2 , S(O) 2 N(R a ), O, OR b , R b O, N(R a )R b , R b N(R a ), R b N(R a )C(O), C(O)N(R a )R b , R b N(R a )S(O) 2 , N(R a )C(O)R b , R b C(O)N(R a ), R b N(R a ), R b N(R a )S(O) 2 , S(O) 2 R b , R b S(O) 2 , or N(R a ); and
D is —CN, —C(O)N(R a ) 2 or N(R a ) 2 ; or
D is —O-optionally substituted (C 1 -C 6 )alkyl, optionally substituted aryl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted heterocyclyl or optionally substituted heteroaryl;
wherein D may be optionally substituted by one or more CN, halogen, OH, —C(O)— (C 1 -C 6 )alkyl, —C(O)N(R a ) 2 , —O—(C 1 -C 6 )alkyl, —N(R a )S(O) 2 R a , —S—(C 1 -C 6 )alkyl, —S(O)—(C 1 -C 6 )alkyl, —S(O) 2 —(C 1 -C 6 )alkyl or —S(O) 2 N(R a ) 2 .
4. The compound of claim 3 wherein
Y is A-D wherein A is connected to X wherein
A is a bond, C(O), C(O)R b , R b C(O), S(O) 2 , optionally substituted (C 1 -C 6 )alkylene, N(R a )S(O) 2 R b , N(R a )C(O), C(O)N(R a ), N(R a )S(O) 2 , S(O) 2 N(R a ), O, OR b , R b O, N(R a )R b , R b N(R a ), R b N(R a )C(O), C(O)N(R a )R b , R b N(R a )S(O) 2 , N(R a )C(O)R b , R b C(O)N(R a ), R b N(R a ), R b N(R a )S(O) 2 , S(O) 2 R b , R b S(O) 2 , or N(R a ); and
D is —CN, —C(O)N(R a ) 2 or —N(R a ) 2 ; or
D is, —O-optionally substituted (C 1 -C 6 )alkyl, optionally substituted aryl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted heterocyclyl or optionally substituted heteroaryl;
wherein D may be optionally substituted by one or more —CN, halogen, —OH, —C(O)— (C 1 -C 6 )alkyl, —C(O)N(R a ) 2 , —O—(C 1 -C 6 )alkyl, —N(R a )S(O) 2 R a , —S—(C 1 -C 6 )alkyl, —S(O)—(C 1 -C 6 )alkyl, —S(O) 2 —(C 1 -C 6 )alkyl or —S(O) 2 N(R a ) 2 .
5. The compound of claim 3 wherein
Y is —S(O) 2 N(R a ) 2 , —N(R a )S(O) 2 , —OR a , —C(O)N(R a ) 2 , —N(R a )C(O)R a , —N(R a ) 2 , —CH 3 or —CH 2 NH 2 ; or
Y is A-D wherein
A is a bond, C(O), S(O) 2 , optionally substituted (C 1 -C 6 )alkylene, N(R a )S(O) 2 R b , N(R a )C(O), C(O)N(R a ), N(R a )S(O) 2 , S(O) 2 N(R a ), O, OR b , R b N(R a ), R b N(R a )C(O), C(O)N(R a )R b , R b N(R a )S(O) 2 , N(R a )C(O)R b , or R b C(O)N(R a ), and
D is CN, —C(O)N(R a ) 2 , N(R a ) 2 , or —O-optionally substituted (C 1 -C 6 )alkyl; or
D is optionally substituted aryl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted heterocyclyl or optionally substituted heteroaryl;
wherein D may be optionally substituted by one or more —CN, halogen, —OH, —C(O)— (C 1 -C 6 )alkyl, —C(O)N(R a ) 2 , —O—(C 1 -C 6 )alkyl, —N(R a )S(O) 2 R a , —S—(C 1 -C 6 )alkyl, —S(O)—(C 1 -C 6 )alkyl, —S(O) 2 —(C 1 -C 6 )alkyl or —S(O) 2 N(R a ) 2 .
6. The compound of claim 5 wherein
W is optionally substituted (C 1 -C 6 )alkylene;
X is a bond, phenylene, optionally substituted (C 3 -C 6 )cycloalkylene, or optionally substituted piperidinyl;
Y is —S(O) 2 N(R a ) 2 , —N(R a )S(O) 2 , —OR a , —C(O)N(R a ) 2 , —N(R a )C(O)R a , —N(R a ) 2 , or optionally substituted (C 1 -C 6 )alkyl; or
Y is A-D wherein A is connected to X wherein
A is a bond, C(O), N(R a )C(O), or R b N(R a )C(O); and
D is —CN, —C(O)N(R a ) 2 , —N(R a ) 2 , or —O-optionally substituted (C 1 -C 6 )alkyl.
7. The compound of claim 6 wherein
R 4 is H or optionally substituted (C 1 -C 4 )alkyl;
R 5 is -G-J wherein G is connected to the nitrogen atom and wherein
G is a bond, pyrazole or phenylene;
wherein the phenylene is optionally substituted with CH 3 ; and
J is H, optionally substituted (C 1 -C 3 )alkyl, —OH, —OCH 3 , —C(O)Ra, —C(O)N(R a ) 2 , —SR a —, —S(O) 2 -optionally substituted (C 1 -C 3 )alkyl, —S(O) 2 —N(R a ) 2 , -optionally substituted phenyl, optionally substituted thiomorpholinyl or optionally substituted piperazinyl;
wherein R a is independently H or optionally substituted (C 1 -C 6 )alkyl.
8. The compound of claim 2 wherein
R 1 is
wherein R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are independently H, —CN, —OH, optionally substituted (C 1 -C 6 )alkyl, —O-optionally substituted (C 1 -C 6 )alkyl or optionally substituted (C 3 -C 10 )cycloalkyl; or
R 13 and R 16 together form an optionally substituted carbocyclic ring or an optionally substituted heterocyclic ring; or
R 11 and R 12 together form an optionally substituted carbocyclic ring, an optionally substituted heterocyclic ring or an optionally substituted spirocyclic ring; or
R 11 and R 13 together form an optionally substituted carbocyclic ring or optionally substituted heterocyclic ring; or
R 16 and R 17 together form an optionally substituted carbocyclic ring or optionally substituted heterocyclic ring; or
R 15 and R 17 together with the nitrogen to which R 17 is attached form heterocyclic ring fused to Ring 1; or
R 17 and R 18 are independently H, —S(O) 2 -optionally substituted (C 3 -C 10 )cycloalkyl, —S(O) 2 -optionally substituted aryl, —S(O) 2 -optionally substituted (C 1 -C 6 )alkyl, —S(O) 2 , —S(O) 2 -optionally substituted heterocyclyl, —S(O) 2 -optionally substituted heteroaryl, —C(O)-optionally substituted (C 3 -C 10 )cycloalkyl, —C(O)-optionally substituted aryl, —C(O)-optionally substituted (C 1 -C 6 )alkyl, —C(O)-optionally substituted heterocyclyl- or —C(O)-optionally substituted heteroaryl; or
R 17 and R 18 form a heterocyclic ring together with the nitrogen to which they are attached.
9. The compound of claim 8 wherein R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are independently H, CN, OH, optionally substituted (C 1 -C 6 )alkyl, —O-optionally substituted (C 1 -C 6 )alkyl or optionally substituted (C 3 -C 10 )cycloalkyl.
10. The compound of claim 8 wherein R 13 and R 16 together form an optionally substituted carbocyclic ring or an optionally substituted heterocyclic ring.
11. The compound of claim 8 wherein R 11 and R 12 together form an optionally substituted carbocyclic ring, an optionally substituted heterocyclic ring or an optionally substituted spirocyclic ring.
12. The compound of claim 8 wherein R 16 and R 17 together form an optionally substituted carbocyclic ring or optionally substituted heterocyclic ring.
13. The compound of claim 8 wherein R 15 and R 17 together with the nitrogen to which R 17 is attached form heterocyclic ring fused to Ring 1.
14. The compound of claim 8 wherein R 17 and R 18 are independently H, —S(O) 2 -optionally substituted (C 3 -C 10 )cycloalkyl, —S(O) 2 -optionally substituted aryl, —S(O) 2 -optionally substituted (C 1 -C 6 )alkyl, —S(O) 2 , —S(O) 2 -optionally substituted heterocyclyl, —S(O) 2 -optionally substituted heteroaryl, —C(O)-optionally substituted (C 3 -C 10 )cycloalkyl, —C(O)-optionally substituted aryl, —C(O)-optionally substituted (C 1 -C 6 )alkyl, —C(O)-optionally substituted heterocyclyl- or —C(O)-optionally substituted heteroaryl; or
R 17 and R 18 form a heterocyclic ring together with the nitrogen to which they are attached.
15. The compound of claim 8 wherein R 5 is -G-J wherein G is connected to the nitrogen atom and wherein
G is a bond, optionally substituted (C 3 -C 10 )cycloalkylene, pyrazole or phenylene optionally substituted with CH 3 ; and
J is H, optionally substituted (C 1 -C 6 )alkyl, —OR a , —C(O)R a , —SR a —, —S(O) 2 —R a , —S(O) 2 —N(R a ) 2 , —S(O) 2 —NH—C(O)—R a , optionally substituted heteroaryl, or optionally substituted morpholinyl, optionally substituted thiomorpholinyl or optionally substituted piperazinyl;
wherein R a is independently H, deuterium, optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, or optionally substituted heteroaryl; and
R b is independently optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl.
16. The compound of claim 1 wherein the compound is
tert-butyl-cis-4-((6-(4-methyl-3-sulfamoylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate;
tert-butyl((1R,4R)-4-((6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexyl)methylcarbamate;
3-(1-(3-(N,N-dimethylsulfamoyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-N,N-dimethylbenzenesulfonamide;
tert-butyl ((1R,4R)-4-((6-(3-sulfamoylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexyl)methylcarbamate;
tert-butyl(1R,4R)-4-((6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamat;
tert-butyl 4-(6-(4-methyl-3-sulfamoylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate;
tert-butyl 4-(6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate;
tert-butyl 4-(6-(4-methyl-3-sulfamoylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexylcarbamate;
5-(1-((cis-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-2-methylbenzenesulfonamide;
5-(1-(((1R,4R)-4-(aminomethyl)cyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-2-methylbenzenesulfonamide;
1-(((1R,4R)-4-(aminomethyl)cyclohexyl)methyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
1-(((1R,4R)-4-aminocyclohexyl)methyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
N-(4-(4-methylpiperazin-1-yl)phenyl)-1-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
5-(1-(4-aminocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-2-methylbenzenesulfonamide;
1-(((1S,4S)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
1-(((1R,4R)-4-aminocyclohexyl)methyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
2-(4-(1-(((1R,4R)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-1H-pyrazol-1-yl)propan-1-ol;
N-(cis-4-((6-(4-Methyl-3-sulfamoylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexyl)acetamide;
N-(5-1-(((1S,4S)-4-(3,3-dimethylbutanamido)cyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-2-methylphenylsulfonyl)-3,3-dimethylbutanamide;
3,3-dimethyl-N-((1S,4S)-4-((6-(4-methyl-3-sulfamoylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexyl)butanamide;
3-((1-(cyclohexylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)methyl)benzenesulfonamide;
3-((1-(cyclohexylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)methyl)benzenesulfonamide;
N-(1-cyclohexylmethyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3-(1-cyclohexylmethyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylmethyl)-benzenesulfonamide;
1-(cyclohexylmethyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
tert-butyl((1R,4R)-4-((6-(4-cyclohexylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexyl)methylcarbamate;
1-(((1R,4R)-4-(aminomethyl)cyclohexyl)methyl)-N-(4-cyclohexylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
4-(1-(((1R,4R)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-N,N-dimethylbenzenesulfonamide;
4-(1-(((1R,4R)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-N-cyclopropylbenzenesulfonamide;
3-(1-(((1R,4R)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)benzamide;
[1-(4-amino-cyclohexylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-[4-(1,1-dioxo-thiomorpholin-4-yl)-phenyl]-amine;
1-(((1R,4R)-4-aminocyclohexyl)methyl)-N-(4-(methylsulfonyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
2-(4-(1-(((1R,4R)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)phenylsulfonyl)ethanol;
4-(1-(((1R,4R)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-N-(pyridin-3-ylmethyl)benzenesulfonamide;
4-(1-(((1R,4R)-4-aminocyclohexyl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-N-(4-methoxyphenyl)benzenesulfonamide;
4-(1-(pyridin-3-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)benzene sulfonamide;
N-(4-(4-methylpiperazin-1-yl)phenyl)-1-(pyridin-3-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;
[4-(1,1-dioxo-thiomorpholin-4-yl)-phenyl]-(1-pyridin-3-ylmethyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-amine;
N1-(3-chlorophenyl)-N4-(1-(pyridin-3-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)benzene-1,4-diamine;
N1-(2-methoxyphenyl)-N4-(1-(pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)benzene-1,4-diamine;
2-(6-(4-(2-methoxyphenylamino)phenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-N-methylbenzene sulfonamide;
N1-(1-(cyclohexylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-N4-phenylbenzene-1,4-diamine;
1-(cyclohexylmethyl)-N-(4-(morpholinosulfonyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine; or
N1-(1-(cyclohexylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-N4,N4-dimethylbenzene-1,4-diamine.
17. The compound
2-methyl-5-(4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)phenylamino)benzenesulfonamide;
2-methyl-5-(1-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)benzenesulfonamide;
N-(2-methoxyphenyl)-1-(pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine.