Morpholino pyrimidine derivatives and their use in therapy

A compound of formula (I)

• or a salt, ester or prodrug thereof;
• wherein
• m is 0, 1, 2, 3 or 4;
• X is a linker group selected from —CR4═CR5—, —CR4═CR5CR6R7—, —CR6R7CR5═CR4—, —C≡C—, —C≡CCR6R7—, —CR6R7C≡C—, —NR4CR6R7—, —OCR6R7—, —SCR6R7—, —S(O)CR6R7—, —S(O)2CR6R7—, —C(O)NR4CR6R7—, —NR4C(O)CR6R7—, —NR4C(O)NR5CR6R7—, —NR4S(O)2CR6R7—, —S(O)2NR4CR6R7—, —C(O)NR4—, —NR4C(O)—, —NR4C(O)NR5—, —S(O)2NR4— and —NR4S(O)2—;
• 1Y and Y2 are independently N or CR8 provided that one of 1Y and Y2 is N and the other is CR8;
• R1 is a group selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, carbocyclylC1-6alkyl, heterocyclyl and heterocyclylC1-6alkyl, which group is optionally substituted by one or more substituent group selected from halo, cyano, nitro, R9, —OR9, —SR9, —SOR9, —SO2R9, —COR9, —CO2R9, —CONR9R10, —NR9R10, —NR9COR10, —NR9CO2R10, —NR9CONR10R15, —NR9COCONR10R15 and —NR9SO2R10;
• R2 is a group selected from C1-6alkyl, carbocyclyl and heterocyclyl which group is optionally substituted by one or more substituent group independently selected from halo, cyano, nitro,
• —R11, —OR11, —SR11, —SOR11, —SO2R11, —COR11, —CO2R11, —CONR11R12, —NR11R12, —NR11COR12, and —NR11COCONR12R16;
• each R3, when present, is independently selected from halo, cyano, nitro, —R13, —OR13, —SR13, —SOR13, —SO2R13, —COR13, —CO2R13, —CONR13R14, —NR13R14, —NR13COR14;
• —NR13CO2R14 and —NR13SO2R14;
• R4 and R5 are independently hydrogen or C1-6alkyl;
• or R1 and R4 together with the atom or atoms to which they are attached form a 5- to 10-membered carbocyclic or heterocyclic ring wherein 1, 2 or 3 ring carbon atoms is optionally replaced with N, O or S and which ring is optionally substituted by one or more substituent groups selected from halo, cyano, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, hydroxyC1-6alkyl, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxyC1-6alkoxy, amino, C1-6alkylamino, bis(C1-6alkyl)amino, aminoC1-6alkyl, (C1-6alkyl)aminoC1-6alkyl, bis(C1-6alkyl)aminoC1-6alkyl, cyanoC1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, C1-6alkylsulfonyl(C1-6alkyl)amino, sulfamoyl, C1-6alkylsulfamoyl, bis(C1-6alkyl)sulfamoyl, C1-6alkanoylamino, C1-6alkanoyl(C1-6alkyl)amino, carbamoyl, C1-6alkylcarbamoyl and bis(C1-6alkyl)carbamoyl;
• R6 and R7 are independently selected from hydrogen, halo, cyano, nitro and C1-6alkyl;
• R8 is selected from hydrogen, halo, cyano and C1-6alkyl;
• R9 and R10 are independently hydrogen or a group selected from C1-6alkyl, carbocyclyl, carbocyclylC1-6alkyl, heterocyclyl and heterocyclylC1-6alkyl which group is optionally substituted by one or more substituent groups selected from halo, cyano, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, hydroxyC1-6alkyl, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxyC1-6alkoxy, amino, C1-6alkylamino, bis(C1-6alkyl)amino, aminoC1-6alkyl, (C1-6alkyl)aminoC1-6alkyl, bis(C1-6alkyl)aminoC1-6alkyl, cyanoC1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, C1-6alkylsulfonyl(C1-6alkyl)amino, sulfamoyl, C1-6alkylsulfamoyl, bis(C1-6alkyl)sulfamoyl, C1-6alkanoylamino, C1-6alkanoyl(C1-6alkyl)amino, carbamoyl, C1-6alkylcarbamoyl and bis(C1-6alkyl)carbamoyl;
• R11 and R12 are independently hydrogen or a group selected from C1-6alkyl, carbocyclyl, carbocyclylC1-6alkyl, heterocyclyl and heterocyclylC1-6alkyl which group is optionally substituted by one or more substituent groups selected from halo, cyano, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, hydroxyC1-6alkyl, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxyC1-6alkoxy, amino, C1-6alkylamino, bis(C1-6alkyl)amino, aminoC1-6alkyl, (C1-6alkyl)aminoC1-6alkyl, bis(C1-6alkyl)aminoC1-6alkyl, cyanoC1-6alkyl, C1-6alkylsulfonyl, C1-6alkanoylamino, C1-6alkanoyl(C1-6alkyl)amino, carbamoyl, C1-6alkylcarbamoyl and bis(C1-6alkyl)carbamoyl;
• R13, R14, R15 and R16 are independently hydrogen or a group selected from C1-6alkyl, carbocyclyl, carbocyclylC1-6alkyl, heterocyclyl and heterocyclylC1-6alkyl which group is optionally substituted by one or more substituent groups selected from halo, cyano, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, hydroxyC1-6alkyl, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxyC1-6alkoxy, amino, C1-6alkylamino, bis(C1-6alkyl)amino, aminoC1-6alkyl, (C1-6alkyl)aminoC1-6alkyl, bis(C1-6alkyl)aminoC1-6alkyl, cyanoC1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, C1-6alkylsulfonyl(C1-6alkyl)amino, sulfamoyl, C1-6alkylsulfamoyl, bis(C1-6alkyl)sulfamoyl, C1-6alkanoylamino, C1-6alkanoyl(C1-6alkyl)amino, carbamoyl, C1-6alkylcarbamoyl and bis(C1-6alkyl)carbamoyl;
• provided that when X is —C(O)NH—, R1 is not the group
• for use as a medicament in the treatment of proliferative disease.