Inhibitors of Protein Kinases

A compound of general Formula I:

• or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein:
• A is N and B is CH, C(C1-4alkyl) or C(NH2),
• Ra is H or methyl;
• R1 is selected from the group consisting of:
• C1-8alkyl;
• —NR6R7, C1-6 alkyl-NR6R7, R20, —C1-6alkyl-R20, —C1-6 alkyl-C(O)OR4, C1-6alkyl-C(O)R4, —NR10—(C1-6 alkyl)-NR6R7, —NR10—(C1-6 alkyl)-R20, —NR10—(C1-6 alkyl)-C(O)OR4, —NR10R20, O—(C1-6 alkyl)-NR6R7, —O—(C1-6alkyl)-R20, —O—(C1-6alkyl)-C(O)OR4, —OR20, C1-6 alkyl-OR20, C1-6 alkyl-SR20, C1-C6 alkyl-NR10R20, (C1-6 alkyl)-O—(C1-6 alkyl)-R20, (C1-6 alkyl)-S—(C1-6 alkyl)-R20, C(O)R20;
• where alkyl moieties may be straight or branched and may be substituted by one or more substituents chosen from halo, methoxy, ethoxy NR6R7 or a nitrogen-containing heterocyclic ring;
• R4 represents H or C1-4-alkyl;
• R6 and R7 are each independently selected from the group consisting of H, C1-6alkyl, hydroxy-C2-6alkyl-;
• R10 represents H or C1-4alkyl;
• R20 is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl and may be substituted by one or more substituents selected from:
• C1-6alkyl, C2-6alkenyl, C2-6alkynyl any of which may be substituted by one or more halo or OH substituents;
• R21, —C1-4 alkyl-R21;
• OR21, O(C1-4 alkyl)R21, SR21, SOR21, SO2R21, C1-4 alkyl-OR21,
• —O(C2-6alkenyl), —O(C2-6alkynyl), any of which may be substituted by one or more halo or OH substituents;
• OR22, —SR22—SOR22, —SO2R22, —C(O)R22, —C(O)OR22, —C1-4 alkyl-O—R22, —C1-4alkyl-O—C1-4alkyl-O—-R22, C1-4alkyl-C(O)R22, —C1-4alkyl-C(O)R22, NR11C(O)OR22, NR11C(O)R22, —SO2—NR11R12, —C(O)—NR11R12, alkyl-C(O)—NR11R12, —NH—SO2R15, —N(C1-4alkyl)-SO2R15, —(C1-4alkyl)NR11R12, NR11R12, —(C1-6alkyl)NR11R12, nitro, halogen, cyano and hydroxyl;
• and when R20 is carbocyclyl or heterocyclyl or an aromatic group in which an aromatic ring is fused to a non-aromatic ring, R20 may additionally be substituted by oxo;
• R21 is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl and may be substituted by one or more substituents as defined below;
• when R21 is an aryl or heteroaryl group, it may be substituted by one or more substituents selected from:
• wherein phenyl is optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy;
• when R21 is a carbocyclic or heterocyclic group it may be substituted by one or more substituents selected from methyl, oxo or halogen;
• R22 is hydrogen or C1-6 alkyl optionally substituted by halo or hydroxyl;
• R11 and R12 each independently represent a substituent selected from H or C1-4alkyl or R11 and R12 are joined such that together they form a 3-8 membered non-aromatic ring;
• R15 represents H or C1-4alkyl;
• R2 represents H, C1-6alkyl or NH2;
• each R3 independently represents a substituent selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-8cycloalkyl (optionally substituted by methyl, oxo or halogen), phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —C1-6alkyl-OH, —Cl-4alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), C1-6alkoxy-, C1-6alkenyloxy, C3-6alkynyloxy-, C1-6haloalkoxy-, —O—C3-8cycloalkyl, —O—C1-4alkyl-C3-8cycloalkyl, —O-phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —O—C1-4alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —S(C1-6alkyl), —SO(C1-6alkyl), —SO2C1-6alkyl, —SO2C3-8cycloalkyl, —SO2—NR31R32, —C(O)C1-6alkyl, —C(O)C3-8cycloalkyl, —C(O)OH, —C(O)OC1-6alkyl, —C(O)—NR31R32, —C1-4alkyl-O—C1-4alkyl, —C1-4alkyl-O—C1-4alkyl-OH, —C1-4alkyl-O—C1-4alkyl-O—C1-4alkyl, —C1-4alkyl-O—C3-7cycloalkyl, —C1-4alkyl-C(O)C1-6alkyl, —C1-4alkyl-C(O)OH, —C1-4alkyl-C(O)OC1-4alkyl, —C1-4alkyl-C(O)—NR31R32, —NH—SO2R33, —N(C1-4alkyl)-SO2R33, —(C1-4alkyl)NR31R32, —NR31R32, —(C1-6alkyl)NR31R32, nitro, halogen, cyano, hydroxyl;
• R31 and R32 each independently represent a substituent selected from H, C1-4alkyl or C1-4haloalkyl or R31 and R32 are joined such that together they form a 3-8 membered non-aromatic ring;
• R33 represents H or C1-4alkyl;
• x represents the number of independently selected R3 substituents on the phenyl ring, in the range 0-4.