Kinase inhibitors

A pharmaceutical formulation comprising a pharmaceutically acceptable adjuvant, diluent or carrier and a compound having the structure of Formula Ia,

• or pharmaceutically acceptable salt, solvate or isotopic derivative thereof, wherein:
• X represents halo;
• Ak represents C1-6 alkyl optionally substituted by one or more fluorine atoms;
• R1 and R2 each independently represents H, C1-6 alkyl, C3-7 cycloalkyl, aryl, heteroaryl, or heterocyclyl, which latter five groups are optionally substituted by one or more substituents selected from halo, cyano, —C(O)OH, oxo, —NR3SO2R4, —N═S(O)(R4)2, —S(O)mR5, —P(O)(R4)2, —C(O)NR5R6, —S(O)2NR5R6, —(OCH2CH2)0-4OR5, —(CH2)0-4—NR5R6, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, aryl, heteroaryl or heterocyclyl, which latter seven groups are optionally substituted by one or more substituents selected from halo, cyano, —C(O)OH, C1-4 alkyl, C1-4 alkoxy, oxo and hydroxy;
• or R1 and R2, together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated or partially unsaturated and which heterocyclic group contains one N atom (the atom to which R1 and R2 are attached) and, optionally, one or more further heteroatoms selected from O, S and N, and which heterocyclic group is optionally fused to a benzene or heteroaromatic ring, and which heterocyclic group is optionally substituted by one or more substituents selected from halo, hydroxy, oxo, —C(O)OH, —NR3SO2R4, —S(O)mR5, —C(O)NR5R6, —(CH2)0-4—NR5R6, —(OCH2CH2)0-4OR5, C1-4 alkyl, C1-4 alkoxy, aryl, heteroaryl, and heterocyclyl, which latter five groups are optionally substituted by one or more substituents selected from halo, cyano, —C(O)OH, C1-4 alkyl, C1-4 alkoxy, oxo and hydroxy;
• R3 represents H or C1-4 alkyl optionally substituted by one or more substituents selected from halo, hydroxy and C1-2 alkoxy;
• R4 represents C1-4 alkyl, C3-7 cycloalkyl, aryl, heteroaryl or heterocyclyl, which latter five groups are optionally substituted by one or more substituents selected from halo, cyano, —C(O)OH, C1-4 alkyl, oxo, hydroxy and C1-4 alkoxy;
• R5 and R6 each independently represent H, C1-6 alkyl, C3-7 cycloalkyl, aryl, heteroaryl, or heterocyclyl, which latter five groups are optionally substituted by one or more substituents selected from halo, cyano, —C(O)OH, oxo, hydroxy, C1-4 alkyl, C1-4 alkoxy, —S(O)pR7, —C(O)NRaRb and —(CH2)0-4—NRaRb, or
• [C(R6b)(R6c)CH2Z]1-12—CH2CH2—R6a or —C(R6b)(R6c)—[C1-5 alkylene]-R6a;
• or R5 and R6, together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated or partially unsaturated and which heterocyclic group contains one N atom (the atom to which R5 and R6 are attached) and, optionally, one or more further heteroatoms selected from O, S and N, and which heterocyclic group is optionally substituted by one or more substituents selected from halo, hydroxy, oxo, —C(O)OH, —S(O)pR7, —C(O)NRaRb, —(CH2)0-4—NRaRb, —(OCH2CH2)0-4ORc, C1-4 alkyl, C1-4 alkoxy, aryl, heteroaryl and heterocyclyl, which latter five groups are optionally substituted by one or more substituents selected from halo, cyano, —C(O)OH, C1-4 alkyl, C1-4 alkoxy, oxo and hydroxy;
• Z represents, independently upon each occurrence, —O—, —C(O)N(R8)— or —N(R8)C(O)—;
• R6a represents —OR7a, —S(O)pR7, —N(R7b)R7c or —C(O)OH;
• R6b, R6c and R8 independently represent H or methyl;
• Ra, Rb and Rc independently represent H or C1-4 alkyl optionally substituted by one or more substituents selected from halo, hydroxy and —C(O)OH,
• or Ra and Rb, together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic and which heterocyclic group contains one N atom (the atom to which Ra and Rb are attached) and, optionally, one or more further heteroatoms selected from O, S and N, and which heterocyclic group is optionally substituted by one or more substituents selected from halo, hydroxy, oxo, —C(O)OH, C1-4 alkyl, C1-4 alkoxy and C1-4 hydroxyalkyl;
• R7 represents C1-4 alkyl optionally substituted by one or more substituents selected from halo, hydroxy and C1-4 alkoxy;
• R7a to R7c independently represent H or C1-4 alkyl optionally substituted by one or more halo atoms or by —C(O)OH,
• or R7b and/or R7c represents —[Ca alkylene]-[Cb alkylene]-OR7d,
• or R7b and R7c together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic and which heterocyclic group contains one N atom (the atom to which R7b and R7c are attached) and, optionally, one or more further heteroatoms selected from O, S and N, and which heterocyclic group is optionally substituted by one or more substituents selected from halo, hydroxy, oxo, —C(O)OH, C1-4 alkyl, C1-4 alkoxy and C1-4 hydroxyalkyl;
• a and b independently represent an integer selected from 1, 2 and 3, wherein the sum of a and b is 2, 3 or 4;
• R7d represents H or C1-4 alkyl optionally substituted by one or more halo atoms:
• and
• m and p represent, independently upon each occurrence, 0, 1 or 2.