Pyrazolo[3,4-d]pyrimidine compounds

A compound of Formula (I)

• a pharmaceutically acceptable salt or stereoisomer thereof wherein
• R1 is —W—X—Y wherein W is directly attached to the nitrogen of the pyrazolyl ring;
• W is phenylene, optionally substituted (C1-C6)alkylene, optionally substituted bridged (C2-C10)heterocyclylene, (C3-C6)cycloalkylene, optionally substituted heterocyclylene or optionally substituted heteroarylene;
• X is a bond, phenylene, optionally substituted (C3-C6)cycloalkylene, optionally substituted piperidinyl or optionally substituted heteroarylene;
• Y is deuterium, —C(O)Ra, —S(O)2N(Ra)2, —N(Ra)S(O)2, —ORa, —N(Ra)S(O)2Ra, —C(O)N(Ra)2, —N(Ra)C(O)Ra, —N(Ra)2, S(O)2Ra, —CH3, —CH2NH2, -optionally substituted (C1-C6)alkylene, —N(Ra)C(O)O—Ra, or optionally substituted (C1-C6)alkyl, provided that when W and X are both bonds then Y is not oxo, —N(Ra)S(O)2Ra, —N(Ra)C(O)Ra or —N(Ra)2;
• or
• Y is A-D wherein A is connected to X wherein
• A is a bond, C(O), C(O)Rb, RbC(O), S(O)2, optionally substituted (C1-C6)alkylene, N(Ra)S(O)2Rb, RbS(O)2N(Ra), N(Ra)C(O), C(O)N(Ra), N(Ra)S(O)2, S(O)2N(Ra), O, ORb, RbO, N(Ra)Rb, RbN(Ra), RbN(Ra)C(O), C(O)N(Ra)Rb, RbN(Ra)S(O)2, S(O)2N(Ra)Rb, N(Ra)C(O)Rb, RbC(O)N(Ra), RbN(Ra), S(O)2Rb, RbS(O)2, and N(Ra);
• and
• D is —CN, —C(O)N(Ra)2 or N(Ra)2;
• or
• D is —O-optionally substituted (C1-C6)alkyl, optionally substituted aryl, optionally substituted (C3-C10)cycloalkyl, optionally substituted heterocyclyl or optionally substituted heteroaryl;
• wherein D may be optionally substituted by one or more CN, halogen, —OH, —C(O)Ra, —Ra, —C(O)N(Ra)2, —O—Ra, —N(Ra)S(O)2Ra, —S—Ra, —S(O)—Ra, —S(O)2—Ra or —S(O)2N(Ra)2;
• provided that R1 is not biphenyl, optionally substituted indanyl, optionally substituted indenyl, optionally substituted indolyl or optionally substituted tetrahydrofuranyl;
• or
• R1 is
• wherein R11, R12, R13, R14, R15 and R16 are independently H, CN, OH, optionally substituted (C1-C6)alkyl, —O-optionally substituted (C1-C6)alkyl or optionally substituted (C3-C10)cycloalkyl;
• R17 and R18 are independently H, —S(O)2-optionally substituted (C3-C10)cycloalkyl, —S(O)2-optionally substituted aryl, —S(O)2-optionally substituted (C1-C6)alkyl, —S(O)2, —S(O)2-optionally substituted heterocyclyl, —S(O)2-optionally substituted heteroaryl, —C(O)-optionally substituted (C3-C10)cycloalkyl, —C(O)-optionally substituted aryl, —C(O)-optionally substituted (C1-C6)alkyl, —C(O)-optionally substituted heterocyclyl- or —C(O)-optionally substituted heteroaryl;
• or
• R17 and R18 form a heterocyclic ring together with the nitrogen to which they are attached;
• or
• R2 is H;
• R3 is H;
• R4 is H;
• R5 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 CH3;
• and
• J is H, optionally substituted (C1-C3)alkyl, —ORa, —C(O)Ra, —S(O)2—Rb, —S(O)2—N(Ra)2, optionally substituted thiomorpholinyl or optionally substituted piperazinyl;
• wherein the piperazinyl is optionally substituted with CH3 and provided that J is not triazolyl;
• or
• R4 and R5 fuse to form a (C2-C4)heterocyclic ring which can be optionally substituted;
• Ra is independently H, deuterium, optionally substituted (C1-C6)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
• and
• Rb is independently optionally substituted (C1-C6)alkyl, optionally substituted (C3-C10)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.