Fused Thiophene Derivatives as Kinase Inhibitors

A compound of formula (IA), (IB) or (IC), or a pharmaceutically acceptable salt or solvate thereof:

• wherein
• Y represents oxygen or sulphur;
• R1 and R2 independently represent hydrogen;
• or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl-(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• or
• R1 and R2, when both are attached to the same carbon atom, represent, when taken together with the carbon atom to which they are both attached, C3-7 cycloalkyl or C3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents;
• or
• R1 and R2, when attached to adjacent carbon atoms, represent, when taken together with the carbon atoms to which they are attached, C5-7 cycloalkyl, phenyl or heteroaryl, any of which groups may be optionally benzo-fused and/or substituted by one or more substituents;
• R3 and R4 independently represent hydrogen;
• or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6 C2-6)alkenyl, aryl(C7-6)alkynyl, biaryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, C3-7 heterocycloalkylcarbonyl, heteroaryl, heteroaryl(C1-6)alkyl, heteroaryl-aryl(C1-6)alkyl or aryl-heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• or
• R3 and R4, when both are attached to the same carbon atom, represent, when taken together with the carbon atom to which they are both attached, C3-7 cycloalkyl or C3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents;
• or
• R3 and R4, when attached to adjacent carbon atoms, represent, when taken together with the carbon atoms to which they are attached, C5-7 cycloalkyl, phenyl or heteroaryl, any of which groups may be optionally benzo-fused and/or substituted by one or more substituents;
• R5 represents hydrogen, halogen, cyano, —SRa, —CORe, —CO2Rb or —CONReRd;
• or R5 represents C1-6 alkyl, C2-6 alkenyl, C2-6 alkenylcarbonyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, C3-7 cycloalkyl(C2-6)alkenyl, C3-7 cycloalkyl(C2-6)alkynyl, aryl, aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, biaryl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, C3-7 heterocycloalkyl(C2-6)alkenyl, C3-7 heterocycloalkyl-(C2-6)alkynyl, C3-7 heterocycloalkylcarbonyl(C2-6)alkynyl, C5-9 heterobicycloalkyl-(C2-6)alkynyl, C3-7 heterocycloalkyl-aryl, C3-7 heterocycloalkyl(C1-6)alkyl-aryl, C3-7 heterocycloalkyl-biaryl, heteroaryl, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkylcarbonyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, heteroaroylcarbonyl, C3-7 heterocycloalkyl-heteroaryl, C3-7 heterocycloalkyl-heteroaryl(C2-6)alkynyl, heteroaryl-aryl, heteroaryl-aryl(C1-6)alkyl, aryl-heteroaryl, aryl-heteroaryl(C1-6)alkyl, C3-7 heterocycloalkyl-aryl-heteroaryl, C3-7 heterocycloalkyl(C1-6)alkyl-aryl-heteroaryl, C5-9 heterobicycloalkyl(C1-6)alkyl-aryl-heteroaryl, heteroaryl-aryl-heteroaryl, bi(heteroaryl), C3-7 heterocycloalkylcarbonyl-bi(heteroaryl), aryloxyaryl, aryl(C1-6)alkoxyaryl, heteroaryl(C1-6)alkoxyaryl, aryl(C1-6)alkylaminoaryl, heteroaryl(C1-6)alkylaminoaryl, C3-7 cycloalkylcarbonylaminoaryl, arylcarbonylaminoaryl, aryl(C1-6)alkylcarbonylaminoaryl, C3-7 heterocycloalkylcarbonylaminoaryl, heteroarylcarbonylaminoaryl, aryl-(C3-2)heterocycloalkylcarbonylaminoaryl, arylsulphonylaminoaryl, aryl(C1-6)alkyl-sulphonylaminoaryl, heteroaryl(C1-6)alkylcycloalkylamino-carbonylaminoaryl, arylaminocarbonylaminoaryl, C3-7 heterocycloalkylaminocarbonyl-aminoaryl, C3-7heterocycloalkylaminocarbonylaminoaryl, heteroaryl(C1-6)alkyl-aminocarbonylaminoaryl, C3-7 heterocycloalkylcarbonylcarbonylaminoaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonylcarbonylaminoaryl, arylcarbonylaryl, C3-7 heterocycloalkylcarbonylaryl, C3-7 heterocycloalkylcarbonyl(C1-6)alkylaryl, aryl(C1-6)-alkylaminocarbonylaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonylaryl, heteroaryl-aminocarbonylaryl, heteroaryl(C1-6)alkylaminocarbonylaryl, C3-7 heterocycloalkylamino-carbonyl(C1-6)alkylaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonyl(C1-6)alkylaryl, heteroarylaminocarbonyl(C1-6)alkylaryl, heteroaryl(C1-6)alkylaminocarbonyl(C1-6)alkyl-aryl, arylaminoheteroaryl, C3-7 heterocycloalkylamino-aryl-heteroaryl, C3-7 heterocycloalkylcarbonylamino-aryl-heteroaryl, C3-7 heterocycloalkylaminocarbonyl-amino-aryl-heteroaryl, C3-7 heterocycloalkylcarbonyl-aryl-heteroaryl, C3-7 heterocycloalkyl(C1-6)alkylcarbonyl-aryl-heteroaryl, C5-9 heterobicycloalkylcarbon-aryl-heteroaryl, C3-7 heterocycloalkylcarbonyl(C1-6)alkyl-aryl-heteroaryl, C3-7 heterocycloalkyl-aminocarbonyl-aryl-heteroaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonyl-aryl-heteroaryl or C3-7 heterocycloalkylaminocarbonyl(C1-6)alkyl-aryl-heteroaryl, any of which groups may be optionally substituted by one or more substituents;
• Ra represents C1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
• Rb represents hydrogen;
• or optionally substituted C1-6alkyl;
• Rc represents hydrogen;
• or C1-6 alkyl, aryl, aryl(C1-6)alkyl, heteroaryl, heteroaryl(C1-6)alkyl or (aryl)(heteroaryl)(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• Rd represents hydrogen or C1-6 alkyl;
• Re represents C1-6 alkyl;
• and
• R6 and R7 independently represent hydrogen or C1-6 alkyl.

A compound of formula (IIA), or a pharmaceutically acceptable salt or solvate thereof:

• wherein
• —X1— represents a group of formula (a), (b) or (c):
• R5 represents hydrogen, cyano, —SRa, —CORe, —CO2Rb or —CONReRd;
• or R5 represents C1-6 alkyl, C2-6 alkenyl, C2-6 alkenylcarbonyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, C3-7 cycloalkyl(C7-6)alkenyl, C3-7 cycloalkyl(C2-6)alkynyl, aryl, aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, biaryl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, C3-7 heterocycloalkyl(C2-6)alkenyl, C3-7 heterocycloalkyl-(C2-6)alkynyl, C3-7 heterocycloalkylcarbonyl(C2-6)alkynyl, C5-9 heterobicycloalkyl-(C2-6)alkynyl, C3-7 heterocycloalkyl-aryl, C3-7 heterocycloalkyl(C1-6)alkyl-aryl, C3-7 heterocycloalkyl-biaryl, heteroaryl, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkylcarbonyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, heteroarylcarbonyl, C3-7 heterocycloalkyl-heteroaryl, C3-7 heterocycloalkyl-heteroaryl(C2-6)alkynyl, heteroaryl-aryl, heteroaryl-aryl(C1-6)alkyl, aryl-heteroaryl, aryl-heteroaryl(C1-6)alkyl, C3-7 heterocycloalkyl-aryl-heteroaryl, C3-7 heterocycloalkyl(C1-6)alkyl-aryl-heteroaryl, C5-9 heterobicycloalkyl(C1-6)alkyl-aryl-heteroaryl, heteroaryl-aryl-heteroaryl, bi(heteroaryl), C3-7 heterocycloalkylcarbonyl-bi(heteroaryl), aryloxyaryl, aryl(C1-6)alkoxyaryl, heteroaryl(C1-6)alkoxyaryl, aryl(C1-6)alkylaminoaryl, heteroaryl(C1-6)alkylaminoaryl, C3-7 cycloalkylcarbonylaminoaryl, arylcarbonylaminoaryl, aryl(C1-6)alkylcarbonylaminoaryl, C3-7 heterocycloalkylcarbonylaminoaryl, heteroarylcarbonylaminoaryl, aryl-(C3-7)heterocycloalkylcarbonylaminoaryl, arylsulphonylaminoaryl, aryl(C1-6)alkyl-sulphonylaminoaryl, heteroaryl(C1-6)alkylsulphonylaminoaryl, C3-7 cycloalkylamino-carbonylaminoaryl, arylaminocarbonylaminoaryl, C3-7 heterocycloalkylaminocarbonyl-aminoaryl, C3-7 heterocycloalkylaminocarbonylaminoaryl, heteroaryl(C1-6)alkyl-aminocarbonylaminoaryl, C3-7 heterocycloalkylcarbonylcarbonylaminoaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonylcarbonylaminoaryl, arylcarbonylaryl, C3-7 heterocycloalkylcarbonylaryl, C3-7 heterocycloalkylcarbonyl(C1-6)alkylaryl, aryl(C1-6 alkylaminocarbonylaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonylaryl, heteroaryl-aminocarbonylaryl, heteroaryl(C1-6)alkylaminocarbonylaryl, C3-7 heterocycloalkylamino-carbonyl(C1-6)alkylaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonyl(C1-6)alkylaryl, heteroarylaminocarbonyl(C1-6)alkylaryl, heteroaryl(C1-6)alkylaminocarbonyl(C1-6)alkyl-aryl, arylaminoheteroaryl, C3-7 heterocycloalkylamino-aryl-heteroaryl, C3-7 heterocycloalkylcarbonylamino-aryl-heteroaryl, C3-7 heterocycloalkylaminocarbonyl-amino-aryl-heteroaryl, C3-7 heterocycloalkylcarbonyl-aryl-heteroaryl, C3-7 heterocycloalkyl(C1-6)alkylcarbonyl-aryl-heteroaryl, C5-9 heterobicycloalkylcarbonyl-aryl-heteroaryl, C3-7 heterocycloalkylcarbonyl(C1-6)alkyl-aryl-heteroaryl, C3-7 heterocycloalkyl-aminocarbonyl-aryl-heteroaryl, C3-7 heterocycloalkyl(C1-6)alkylaminocarbonyl-aryl-heteroaryl or C3-7 heterocycloalkylaminocarbonyl(C1-6 alkyl aryl heteroaryl, any of which groups may be optionally substituted by one or more substituents;
• Ra represents C1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
• Rb represents hydrogen;
• or optionally substituted C1-6 alkyl;
• Rc represents hydrogen;
• or C1-6 alkyl, aryl, aryl(C1-6)alkyl, heteroaryl, heteroaryl(C1-6)alkyl or (aryl)(heteroaryl)(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• Rd represents hydrogen or C1-6 alkyl;
• Re represents C1-6 alkyl;
• R11 represents hydrogen or optionally substituted C1-6 alkyl;
• and
• R12 represents hydrogen;
• or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• or
• R11 and R12, when taken together with the carbon atom to which they are both attached, represent C3-7 cycloalkyl or C3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents.

A compound of formula (IIB), or a pharmaceutically acceptable salt or solvate thereof:

• wherein;
• —X1— represents a group of formula (a), (b) or (c):
• R11 represents hydrogen or optionally substituted C1-6 alkyl;
• and
• R12 represents hydrogen;
• or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• or
• R11 and R12, when taken together with the carbon atom to which they are both attached, represent C3-7 cycloalkyl or C3-7 heterocycloalkyl, either of which groups may be optionally substituted by one or more substituents;
• and
• R13 represents hydrogen;
• or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, biaryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, C3-7 heterocycloalkylcarbonyl, heteroaryl, heteroaryl(C1-6)alkyl, heteroaryl-aryl(C1-6)alkyl or aryl-heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents.