Imidazopyrazines for use as kinase inhibitors

A compound of formula I,

• wherein:
• R1 represents:
• (a) —N(R1a)R1b,
• in which R1a and R1b are linked together to form, together with the nitrogen atom to which they are necessarily attached, a 5- to 7-membered ring optionally containing a further one or two heteroatoms, optionally containing one or two double bonds, and which ring is optionally substituted by one or more substituents selected from ═O and B1;
• (b) a heterocycloalkyl group (attached to the requisite imidazopyrazine via a carbon atom), optionally substituted by one or more substituents selected from ═O and B2;
• (c) a monocyclic heteroaryl group optionally substituted by one or more substituents selected from B3;
• R2 and R3 independently represent:
• (i) hydrogen;
• (ii) Q1;
• (iii) C1-12 alkyl optionally substituted by one or more substituents selected from ═O, ═S, ═N(R10a) and Q2;
• or
• R2 or R3 may represent a fragment of formula IA,
• m represents 0, 1, 2, 3, 4, 5 or 6;
• each R15 represents hydrogen, halo or C1-6 alkyl optionally substituted by one or more substituents selected from E1;
• or
• the two R15 groups may linked together to form (along with the requisite carbon atom to which those R15 groups are necessarily attached) a 3- to 6-membered (spiro-cyclic) ring, which ring optionally contains one or more double bonds, and optionally contains a further heteroatom selected from nitrogen, sulfur and oxygen, and which ring is optionally substituted by one or more substituents selected from E2;
• Ra and Rb are linked together, along with the requisite nitrogen atom to which they are necessarily attached, to form a first 3- to 7-membered cyclic group, optionally containing one further heteroatom selected from nitrogen, sulfur and oxygen, and which ring:
• (a) is fused to a second ring that is either a 3- to 7-membered saturated heterocycloalkyl group containing one to four heteroatoms selected from oxygen, sulfur and nitrogen, a 3- to 12-membered saturated carbocyclic ring, or an unsaturated 5- to 12-membered carbocyclic or heterocyclic ring;
• (b) comprises a linker group —(C(Rx)2)p— and/or —(C(Rx)2)r—O—(C(Rx)2)s— (wherein p is 1 or 2;
• r is 0 or 1;
• s is 0 or 1;
• and each Rx independently represents hydrogen or C1-6 alkyl), linking together any two non-adjacent atoms of the first 3- to 7-membered ring (i.e. forming a bridged structure);
• or
• (c) comprises a second ring that is either a 3- to 12-membered saturated carbocyclic ring or a 3- to 7-membered saturated heterocycloalkyl group containing one to four heteroatoms selected from oxygen and nitrogen, and which second ring is linked together with the first ring via a single carbon atom common to both rings (i.e. forming a spiro-cycle),
• all of which cyclic groups, defined by the linkage of Ra and Rb, are optionally substituted by one or more substituents selected from ═O and E3;
• R4 represents hydrogen or a substituent selected from halo, —CN, —OR10b, —N(R10b)R11b, —C(O)N(R10b)R11b, —C(O)R10b), C1-6 alkyl and heterocycloalkyl, which latter two groups are optionally substituted by one or more substituents selected from E4 and ═O;
• but wherein at least one of R2, R3 and R4 represents a substituent other than hydrogen;
• R5 represents aryl or heteroaryl (both of which are optionally substituted by one or more substituents selected from E5);
• each Q1 and Q2 independently represents, on each occasion when used herein:
• halo, —CN, —NO2, —N(R10a)R11a, —OR10a, —C(═Y)—R10a, —C(═Y)—OR10a, —C(═Y)N(R10a)R11a, —OC(═Y)—R10a, —OC(═Y)—OR10a, —OC(═Y)—OR10a, —OC(═Y)N(R10a)R11a, —OS(O)2OR10a, —OP(═Y)(OR10a)(OR11a), —OP(OR10a)(OR11a), —N(R12a)C(═Y)R11a, —N(R12a)C(═Y)OR11a, —N(R12a)C(═Y)N(R10a)R11a, —NR12aaS(O)2R10a, —NR12aS(O)2N(R10a)R11a, —S(O)2N(R10a)R11a, —SC(═Y)R10a, —S(O)2R10a, —SR10a, —S(O)R10a, C1-12 alkyl, heterocycloalkyl (which latter two groups are optionally substituted by one or more substituents selected from ═O, ═S, ═N(R10a) and E6), aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from E7);
• each B1, B2 and B3 independently represent halo, —NO2, —CN, —N(R10a)R11a, —OR10a, —C(═Y)—R10a, —C(═Y)—OR10a, —C(═Y)N(R10a)R11a, —N(R12a)C(═Y)R11a, —N(R12a)C(═Y)OR11a, —N(R12a)C(═Y)N(R10a)R11a, —NR12aS(O)2R10a;
• —NR12aS(O)2N(R10a)R11a, —S(O)2N(R10a)R11a, —SC(═Y)R10a, —SC(═Y)OR10a, —S(O)2R10a, C1-12 alkyl, heterocycloalkyl (which latter two groups are optionally substituted by one or more substituents selected from ═O and E8), aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from E9);
• or, any two B1 substituents, when attached to the same carbon atom (thereby forming a spiro-cycle), may be linked together to form, a 3- to 12-membered ring, optionally containing one or more heteroatoms, which ring optionally contains one or more double bonds, and which ring is itself optionally substituted by one or more substituents selected from halo, ═O and C1-3 alkyl optionally substituted by one or more fluoro atoms;
• each R10a, R11a, R12a, R10b and R11b independently represent, on each occasion when used herein, hydrogen, C1-12 alkyl, heterocycloalkyl (which latter two groups are optionally substituted by one or more substituents selected from ═O, ═S, ═N(R20) and E10), aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from E11);
• or
• any relevant pair of R10a, R11a and R12a and/or any pair of R10b and R11b may be linked together to form a 3- to 20-membered ring, optionally containing one or more heteroatoms, optionally containing one or more unsaturations, and which ring is optionally substituted by one or more substituents selected from ═O, ═S, ═N(R20) and E12;
• each E1, E2, E3, E4, E5, E6, E7, E8, E9, E10, E11 and E12 independently represents, on each occasion when used herein:
• (i) Q4;
• (ii) C1-12 alkyl optionally substituted by one or more substituents selected from ═O and
• Q5;
• or
• any two E1, E2, E3, E4, E5, E6, E7, E8, E9, E10, E11 or E12 groups may be linked together to form a 3- to 12-membered ring, optionally containing one or more unsaturations, and which ring is optionally substituted by one or more substituents selected from ═O and J1;
• each Q4 and Q5 independently represent, on each occasion when used herein:
• halo, —CN, —NO2, —N(R20)R21, —OR20, —C(═Y)—R20, —C(═Y)—OR20, —C(═Y)N(R20)R21, —OC(═Y)—R20, —OC(═Y)—OR20, —OC(═Y)N(R20)R21, —OS(O)2OR20, —OP(═Y)(OR20)(OR21), —OP(OR20)(OR21), —N(R22)C(═Y)R21, —N(R22)C(═Y)OR21, —N(R22)C(═Y)N(R20)R21, —NR22S(O)2R20, —NR22S(O)2N(R20)R21, —S(O)2N(R20)R21, —SC(═Y)R20, —S(O)2R20, —SR20, —S(O)R20, C1-6 alkyl, heterocycloalkyl (which latter two groups are optionally substituted by one or more substituents selected from ═O and J2), aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from J3);
• each Y independently represents, on each occasion when used herein, ═O, ═S, ═NR23 or ═N—CN;
• each R20, R21, R22 and R23 independently represent, on each occasion when used herein, hydrogen, C1-6 alkyl, heterocycloalkyl (which latter two groups are optionally substituted by one or more substituents selected from J4 and ═O), aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from J5);
• or
• any relevant pair of R20, R21 and R22, may be linked together to form a 3- to 20-membered ring, optionally containing one or more heteroatoms, optionally containing one or more unsaturations, and which ring is optionally substituted by one or more substituents selected from J6 and ═O;
• each J1, J2, J3, J4, J5 and J6 independently represents, on each occasion when used herein:
• (i) Q7;
• (ii) C1-6 alkyl or heterocycloalkyl, both of which are optionally substituted by one or more substituents selected from ═O and Q8;
• each Q7 and Q8 independently represents, on each occasion when used herein:
• —CN, halo, —N(R50)R51, —OR50, —C(═Ya)—R50, —C(═Ya)—OR50, —C(═Ya)N(R50)R51, —N(R52)C(═Ya)R51, —NR52S(O)2R50, —S(O)2R50, —SR50, —S(O)R50 or C1-6 alkyl optionally substituted by one or more fluoro atoms;
• each Ya independently represents, on each occasion when used herein, ═O, ═S, ═NR53 or ═N—CN;
• each R50, R51, R52 and R53 independently represents, on each occasion when used herein, hydrogen or C1-6 alkyl optionally substituted by one or more substituents selected from fluoro, —OR60 and —N(R61)R62;
• or
• any relevant pair of R50, R51 and R52 may be linked together to form, a 3- to 8-membered ring, optionally containing one or more heteroatoms, optionally containing one or more unsaturations, and which ring is optionally substituted by one or more substituents selected from ═O and C1-3 alkyl;
• R60, R61 and R62 independently represent hydrogen or C1-6 alkyl optionally substituted by one or more fluoro atoms;
• or a pharmaceutically acceptable ester, amide, solvate or salt thereof.