Fused thiophene derivatives as kinase inhibitors
View Patent ↗A series of 5,6-dihydro-1-benzothiophen-7(4H)-one derivatives, and analogues thereof, which are substituted in the 2-position by an optionally substituted morpholin-4-yl moiety, being selective inhibitors of PI3 kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions.
1. A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof:
wherein
—X— represents a group of formula (a), (b), (c), (d), (e), (f) or (g):
Y represents oxygen or sulphur;
R 1 and R 2 independently represent hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl-(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or
R 1 and R 2 , when both are attached to the same carbon atom, represent, when taken together with the carbon atom to which they are both attached, C 3-7 cycloalkyl or C 3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents; or
R 1 and R 2 , when attached to adjacent carbon atoms, represent, when taken together with the carbon atoms to which they are attached, C 5-7 cycloalkyl, phenyl or heteroaryl, any of which groups may be optionally benzo-fused and/or substituted by one or more substituents;
R 3 and R 4 independently represent hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, aryl(C 2-6 )alkenyl, aryl(C 2-6 )alkynyl, biaryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkylcarbonyl, heteroaryl, heteroaryl(C 1-6 )alkyl, heteroaryl-aryl(C 1-6 )alkyl or aryl-heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or
R 3 and R 4 , when both are attached to the same carbon atom, represent, when taken together with the carbon atom to which they are both attached, C 3-7 cycloalkyl or C 3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents; or
R 3 and R 4 , when attached to adjacent carbon atoms, represent, when taken together with the carbon atoms to which they are attached, C 5-7 cycloalkyl, phenyl or heteroaryl, any of which groups may be optionally benzo-fused and/or substituted by one or more substituents;
R 5 represents hydrogen, halogen, cyano, —SR a , —COR e , —CO 2 R b or —CONR c R d ; or R 5 represents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkenylcarbonyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, C 3-7 cycloalkyl(C 2-6 )alkenyl, C 3-7 cycloalkyl(C 2-6 )alkynyl, aryl, aryl(C 1-6 )alkyl, aryl(C 2-6 )alkenyl, aryl(C 2-6 )alkynyl, biaryl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkyl(C 2-6 )alkenyl, C 3-7 heterocycloalkyl-(C 2-6 )alkynyl, C 3-7 heterocycloalkylcarbonyl(C 2-6 )alkynyl, C 5-9 heterobicycloalkyl-(C 2-6 )alkynyl, C 3-7 heterocycloalkyl-aryl, C 3-7 heterocycloalkyl(C 1-6 )alkyl-aryl, C 3-7 heterocycloalkyl-biaryl, heteroaryl, heteroaryl(C 1-6 )alkyl, heteroaryl(C 1-6 )alkylcarbonyl, heteroaryl(C 2-6 )alkenyl, heteroaryl(C 2-6 )alkynyl, heteroaroylcarbonyl, C 3-7 heterocycloalkyl-heteroaryl, C 3-7 heterocycloalkyl-heteroaryl(C 2-6 )alkynyl, heteroaryl-aryl, heteroaryl-aryl(C 1-6 )alkyl, aryl-heteroaryl, aryl-heteroaryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkyl-aryl-heteroaryl, C 5-9 heterobicycloalkyl(C 1-6 )alkyl-aryl-heteroaryl, heteroaryl-aryl-heteroaryl, bi(heteroaryl), C 3-7 heterocycloalkylcarbonyl-bi(heteroaryl), aryloxyaryl, aryl(C 1-6 )alkoxyaryl, heteroaryl(C 1-6 )alkoxyaryl, aryl(C 1-6 )alkylaminoaryl, heteroaryl(C 1-6 )alkylaminoaryl, C 3-7 cycloalkylcarbonylaminoaryl, arylcarbonylaminoaryl, aryl(C 1-6 )alkylcarbonylaminoaryl, C 3-7 heterocycloalkylcarbonylaminoaryl, heteroarylcarbonylaminoaryl, aryl(C 3-7 )heterocycloalkylcarbonylaminoaryl, arylsulphonylaminoaryl, aryl(C 1-6 )alkyl-sulphonylaminoaryl, heteroaryl(C 1-6 )alkylsulphonylaminoaryl, C 3-7 cycloalkylamino-carbonylaminoaryl, arylaminocarbonylaminoaryl, C 3-7 heterocycloalkylaminocarbonyl-aminoaryl, C 3-7 heterocycloalkylaminocarbonylaminoaryl, heteroaryl(C 1-6 )alkyl-aminocarbonylaminoaryl, C 3-7 heterocycloalkylcarbonylcarbonylaminoaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonylcarbonylaminoaryl, arylcarbonylaryl, C 3-7 heterocycloalkylcarbonylaryl, C 3-7 heterocycloalkylcarbonyl(C 1-6 )alkylaryl, aryl(C 1-6 )-alkylaminocarbonylaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonylaryl, heteroaryl-aminocarbonylaryl, heteroaryl(C 1-6 )alkylaminocarbonylaryl, C 3-7 heterocycloalkylamino-carbonyl(C 1-6 )alkylaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonyl(C 1-6 )alkylaryl, heteroarylaminocarbonyl(C 1-6 )alkylaryl, heteroaryl(C 1-6 )alkylaminocarbonyl(C 1-6 )alkyl-aryl, arylaminoheteroaryl, C 3-7 heterocycloalkylamino-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonylamino-aryl-heteroaryl, C 3-7 heterocycloalkylaminocarbonyl-amino-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylcarbonyl-aryl-heteroaryl, C 5-9 heterobicycloalkylcarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonyl(C 1-6 )alkyl-aryl-heteroaryl, C 3-7 heterocycloalkyl-aminocarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonyl-aryl-heteroaryl or C 3-7 heterocycloalkylaminocarbonyl(C 1-6 )alkyl-aryl-heteroaryl, any of which groups may be optionally substituted by one or more substituents;
R a represents C 1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
R b represents hydrogen; or optionally substituted C 1-6 alkyl;
R c represents hydrogen; or C 1-6 alkyl, aryl, aryl(C 1-6 )alkyl, heteroaryl, heteroaryl(C 1-6 )alkyl or (aryl)(heteroaryl)(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents;
R d represents hydrogen or C 1-6 alkyl;
R e represents C 1-6 alkyl; and
R 6 and R 7 independently represent hydrogen or C 1-6 alkyl.
2. A compound of formula (IA), (IB) or (IC), or a pharmaceutically acceptable salt or solvate thereof:
wherein
Y represents oxygen or sulphur;
R 1 and R 2 independently represent hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl-(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or
R 1 and R 2 , when both are attached to the same carbon atom, represent, when taken together with the carbon atom to which they are both attached, C 3-7 cycloalkyl or C 3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents; or
R 1 and R 2 , when attached to adjacent carbon atoms, represent, when taken together with the carbon atoms to which they are attached, C 5-7 cycloalkyl, phenyl or heteroaryl, any of which groups may be optionally benzo-fused and/or substituted by one or more substituents;
R 3 and R 4 independently represent hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, aryl(C 2-6 )alkenyl, aryl(C 2-6 )alkynyl, biaryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkylcarbonyl, heteroaryl, heteroaryl(C 1-6 )alkyl, heteroaryl-aryl(C 1-6 )alkyl or aryl-heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or
R 3 and R 4 , when both are attached to the same carbon atom, represent, when taken together with the carbon atom to which they are both attached, C 3-7 cycloalkyl or C 3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents; or
R 3 and R 4 , when attached to adjacent carbon atoms, represent, when taken together with the carbon atoms to which they are attached, C 5-7 cycloalkyl, phenyl or heteroaryl, any of which groups may be optionally benzo-fused and/or substituted by one or more substituents;
R 5 represents hydrogen, halogen, cyano, —SR a , —COR e , —CO 2 R b or —CONR c R d ; or R 5 represents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkenylcarbonyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, C 3-7 cycloalkyl(C 2-6 )alkenyl, C 3-7 cycloalkyl(C 2-6 )alkynyl, aryl, aryl(C 1-6 )alkyl, aryl(C 2-6 )alkenyl, aryl(C 2-6 )alkynyl, biaryl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkyl(C 2-6 )alkenyl, C 3-7 heterocycloalkyl-(C 2-6 )alkynyl, C 3-7 heterocycloalkylcarbonyl(C 2-6 )alkynyl, C 5-9 heterobicycloalkyl-(C 2-6 )alkynyl, C 3-7 heterocycloalkyl-aryl, C 3-7 heterocycloalkyl(C 1-6 )alkyl-aryl, C 3-7 heterocycloalkyl-biaryl, heteroaryl, heteroaryl(C 1-6 )alkyl, heteroaryl(C 1-6 )alkylcarbonyl, heteroaryl(C 2-6 )alkenyl, heteroaryl(C 2-6 )alkynyl, heteroaroylcarbonyl, C 3-7 heterocycloalkyl-heteroaryl, C 3-7 heterocycloalkyl-heteroaryl(C 2-6 )alkynyl, heteroaryl-aryl, heteroaryl-aryl(C 1-6 )alkyl, aryl-heteroaryl, aryl-heteroaryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkyl-aryl-heteroaryl, C 5-9 heterobicycloalkyl(C 1-6 )alkyl-aryl-heteroaryl, heteroaryl-aryl-heteroaryl, bi(heteroaryl), C 3-7 heterocycloalkylcarbonyl-bi(heteroaryl), aryloxyaryl, aryl(C 1-6 )alkoxyaryl, heteroaryl(C 1-6 )alkoxyaryl, aryl(C 1-6 )alkylaminoaryl, heteroaryl(C 1-6 )alkylaminoaryl, C 3-7 cycloalkylcarbonylaminoaryl, arylcarbonylaminoaryl, aryl(C 1-6 )alkylcarbonylaminoaryl, C 3-7 heterocycloalkylcarbonylaminoaryl, heteroarylcarbonylaminoaryl, aryl-(C 3-7 )heterocycloalkylcarbonylaminoaryl, arylsulphonylaminoaryl, aryl(C 1-6 )alkyl-sulphonylaminoaryl, heteroaryl(C 1-6 )alkylsulphonylaminoaryl, C 3-7 cycloalkylamino-carbonylaminoaryl, arylaminocarbonylaminoaryl, C 3-7 heterocycloalkylaminocarbonyl-aminoaryl, C 3-7 heterocycloalkylaminocarbonylaminoaryl, heteroaryl(C 1-6 )alkyl-aminocarbonylaminoaryl, C 3-7 heterocycloalkylcarbonylcarbonylaminoaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonylcarbonylaminoaryl, arylcarbonylaryl, C 3-7 heterocycloalkylcarbonylaryl, C 3-7 heterocycloalkylcarbonyl(C 1-6 )alkylaryl, aryl(C 1-6 )-alkylaminocarbonylaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonylaryl, heteroaryl-aminocarbonylaryl, heteroaryl(C 1-6 )alkylaminocarbonylaryl, C 3-7 heterocycloalkylamino-carbonyl(C 1-6 )alkylaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonyl(C 1-6 )alkylaryl, heteroarylaminocarbonyl(C 1-6 )alkylaryl, heteroaryl(C 1-6 )alkylaminocarbonyl(C 1-6 )alkyl-aryl, arylaminoheteroaryl, C 3-7 heterocycloalkylamino-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonylamino-aryl-heteroaryl, C 3-7 heterocycloalkylaminocarbonyl-amino-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylcarbonyl-aryl-heteroaryl, C 5-9 heterobicycloalkylcarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonyl(C 1-6 )alkyl-aryl-heteroaryl, C 3-7 heterocycloalkyl-aminocarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonyl-aryl-heteroaryl or C 3-7 heterocycloalkylaminocarbonyl(C 1-6 )alkyl-aryl-heteroaryl, any of which groups may be optionally substituted by one or more substituents;
R a represents C 1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
R b represents hydrogen; or optionally substituted C 1-6 alkyl;
R c represents hydrogen; or C 1-6 alkyl, aryl, aryl(C 1-6 )alkyl, heteroaryl, heteroaryl(C 1-6 )alkyl or (aryl)(heteroaryl)(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents;
R d represents hydrogen or C 1-6 alkyl;
R e represents C 1-6 alkyl; and
R 6 and R 7 independently represent hydrogen or C 1-6 alkyl.
3. A compound of formula (IIA), or a pharmaceutically acceptable salt or solvate thereof:
wherein
—X 1 — represents a group of formula (a), (b) or (c):
R 5 represents hydrogen, halogen, cyano, —SR a , —COR e , —CO 2 R b or —CONR c R d ; or R 5 represents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkenylcarbonyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, C 3-7 cycloalkyl(C 2-6 )alkenyl, C 3-7 cycloalkyl(C 2-6 )alkynyl, aryl, aryl(C 1-6 )alkyl, aryl(C 2-6 )alkenyl, aryl(C 2-6 )alkynyl, biaryl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkyl(C 2-6 )alkenyl, C 3-7 heterocycloalkyl-(C 2-6 )alkynyl, C 3-7 heterocycloalkylcarbonyl(C 2-6 )alkynyl, C 5-9 heterobicycloalkyl-(C 2-6 )alkynyl, C 3-7 heterocycloalkyl-aryl, C 3-7 heterocycloalkyl(C 1-6 )alkyl-aryl, C 3-7 heterocycloalkyl-biaryl, heteroaryl, heteroaryl(C 1-6 )alkyl, heteroaryl(C 1-6 )alkylcarbonyl, heteroaryl(C 2-6 )alkenyl, heteroaryl(C 2-6 )alkynyl, heteroaroylcarbonyl, C 3-7 heterocycloalkyl-heteroaryl, C 3-7 heterocycloalkyl-heteroaryl(C 2-6 )alkynyl, heteroaryl-aryl, heteroaryl-aryl(C 1-6 )alkyl, aryl-heteroaryl, aryl-heteroaryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkyl-aryl-heteroaryl, C 5-9 heterobicycloalkyl(C 1-6 )alkyl-aryl-heteroaryl, heteroaryl-aryl-heteroaryl, bi(heteroaryl), C 3-7 heterocycloalkylcarbonyl-bi(heteroaryl), aryloxyaryl, aryl(C 1-6 )alkoxyaryl, heteroaryl(C 1-6 )alkoxyaryl, aryl(C 1-6 )alkylaminoaryl, heteroaryl(C 1-6 )alkylaminoaryl, C 3-7 cycloalkylcarbonylaminoaryl, arylcarbonylaminoaryl, aryl(C 1-6 )alkylcarbonylaminoaryl, C 3-7 heterocycloalkylcarbonylaminoaryl, heteroarylcarbonylaminoaryl, aryl-(C 3-7 )heterocycloalkylcarbonylaminoaryl, arylsulphonylaminoaryl, aryl(C 1-6 )alkyl-sulphonylaminoaryl, heteroaryl(C 1-6 )alkylsulphonylaminoaryl, C 3-7 cycloalkylamino-carbonylaminoaryl, arylaminocarbonylaminoaryl, C 3-7 heterocycloalkylaminocarbonyl-aminoaryl, C 3-7 heterocycloalkylaminocarbonylaminoaryl, heteroaryl(C 1-6 )alkyl-aminocarbonylaminoaryl, C 3-7 heterocycloalkylcarbonylcarbonylaminoaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonylcarbonylaminoaryl, arylcarbonylaryl, C 3-7 heterocycloalkylcarbonylaryl, C 3-7 heterocycloalkylcarbonyl(C 1-6 )alkylaryl, aryl(C 1-6 )-alkylaminocarbonylaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonylaryl, heteroaryl-aminocarbonylaryl, heteroaryl(C 1-6 )alkylaminocarbonylaryl, C 3-7 heterocycloalkylamino-carbonyl(C 1-6 )alkylaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonyl(C 1-6 )alkylaryl, heteroarylaminocarbonyl(C 1-6 )alkylaryl, heteroaryl(C 1-6 )alkylaminocarbonyl(C 1-6 )alkyl-aryl, arylaminoheteroaryl, C 3-7 heterocycloalkylamino-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonylamino-aryl-heteroaryl, C 3-7 heterocycloalkylaminocarbonyl-amino-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylcarbonyl-aryl-heteroaryl, C 5-9 heterobicycloalkylcarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkylcarbonyl(C 1-6 )alkyl-aryl-heteroaryl, C 3-7 heterocycloalkyl-aminocarbonyl-aryl-heteroaryl, C 3-7 heterocycloalkyl(C 1-6 )alkylaminocarbonyl-aryl-heteroaryl or C 3-7 heterocycloalkylaminocarbonyl(C 1-6 )alkyl-aryl-heteroaryl, any of which groups may be optionally substituted by one or more substituents;
R a represents C 1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
R b represents hydrogen; or optionally substituted C 1-6 alkyl;
R c represents hydrogen; or C 1-6 alkyl, aryl, aryl(C 1-6 )alkyl, heteroaryl, heteroaryl(C 1-6 )alkyl or (aryl)(heteroaryl)(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents;
R d represents hydrogen or C 1-6 alkyl;
R e represents C 1-6 alkyl;
R 11 represents hydrogen or optionally substituted C 1-6 alkyl; and
R 12 represents hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or
R 11 and R 12 , when taken together with the carbon atom to which they are both attached, represent C 3-7 cycloalkyl or C 3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents.
4. A compound of formula (IIB), or a pharmaceutically acceptable salt or solvate thereof:
wherein
—X 1 — represents a group of formula (a), (b) or (c):
R 11 represents hydrogen or optionally substituted C 1-6 alkyl; and
R 12 represents hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or
R 11 and R 12 , when taken together with the carbon atom to which they are both attached, represent C 3-7 cycloalkyl or C 3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents; and
R 13 represents hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, aryl(C 2-6 )alkenyl, aryl(C 2-6 )alkynyl, biaryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkylcarbonyl, heteroaryl, heteroaryl(C 1-6 )alkyl, heteroaryl-aryl(C 1-6 )alkyl or aryl-heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents.
5. A compound as claimed in claim 4 of formula (IIC), or a pharmaceutically acceptable salt or solvate thereof:
wherein
—X 1 — represents a group of formula (a), (b) or (c):
R 11 represents hydrogen or optionally substituted C 1-6 alkyl; and
R 12 represents hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or
R 11 and R 12 , when taken together with the carbon atom to which they are both attached, represent C 3-7 cycloalkyl or C 3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents;
W represents CH or N; and
R 43 represents hydrogen, halogen, cyano, C 1-6 alkyl, hydroxy(C 1-6 )alkyl, trifluoromethyl, aryl(C 1-6 )alkyl, hydroxy, C 1-6 alkoxy, trifluoromethoxy, aryloxy, aryl(C 1-6 )alkoxy, C 1-6 alkylthio, arylsulphonyl, C 1-6 alkylsulphonyloxy, amino, C 2-6 alkylcarbonylamino, C 1-6 alkylsulphonylamino, C 2-6 alkylcarbonyl or aminocarbonyl.
6. A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof, in association with a pharmaceutically acceptable carrier.