2-carbocycloamino-4-imidazolylpyrimidines as agents for the inhbition of cell proliferation

A compound of formula (I):

• wherein:
• Ring A is a 5-7 membered saturated carbocyclic ring wherein 2 atoms of Ring A may optionally be connected by a bridge;
• R1 is selected from carboxy, amino, sulphamoyl, sulphamoylamino, carbamoyl, a group —R6-R7 or a nitrogen linked 4-7 membered saturated ring which optionally contains an additional nitrogen, oxygen or sulphur atom;
• wherein said ring may be optionally substituted on carbon by one or more R8;
• and wherein if said ring contains an additional nitrogen atom that nitrogen may be optionally substituted by R9;
• R2 is selected from halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6 alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6 alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl-R10— or heterocyclyl-R11—;
• wherein R2 may be optionally substituted on carbon by one or more R12;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R13;
• q is 0-4;
• wherein the values of R2 may be the same or different;
• R3 is selected from halo, cyano or amino;
• n is 0 to 2, wherein the values of R3 may be the same or different;
• R4 is selected from ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, t-butyl, cyclopropyl, cyclopropylmethyl, 1-cyclopropylethyl, cyclobutylmethyl, cyclopentyl or cyclobutyl;
• wherein R4 may be optionally substituted on carbon by one or more R14;
• R5 is selected from methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxymethyl, cyclopropylmethyl or cyclopropyl;
• R6 is selected from —O—, —N(R15)—, —C(O)—, —C(O)O—, —N(R16)C(O)—, —C(O)N(R17)—, —N(R18)C(O)O—, —N(R19)C(O)N(R20)—, —S(O)r, —OC(O)N(R21)SO2—, —N(R22)SO2N(R23)—, —SO2N(R24)—, —N(R25)SO2—, —C(O)N(R39)SO2— or —SO2N(R40)C(O)—;
• wherein R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R39 and R40 are independently hydrogen or C1-6alkyl optionally substituted by one or more R26 and r is 0-2;
• R7 is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl or heterocyclyl;
• wherein R7 may be optionally substituted on carbon by one or more R27;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R28;
• R8, R12, R26 and R27 are independently selected from halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl-R29— or heterocyclyl-R30—;
• wherein R8, R12, R26 and R27 independently of each other may be optionally substituted on carbon by one or more R31;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R32;
• R9, R13, R28 and R32 are independently selected from C1-6alkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
• wherein R9, R13, R28 and R32 independently of each other may be optionally substituted on carbon by one or more R33;
• and
• R10, R11, R29 and R30 are independently selected from a direct bond, —O—, —N(R34)—, —C(O)—, —N(R35)C(O)—, —C(O)N(R36)—, —S(O)s—, —SO2N(R37)— or —N(R38)SO2—;
• wherein R34, R35, R36, R37 and R38 are independently selected from hydrogen or C1-6alkyl and s is 0-2;
• R14 is selected from halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl and C1-6alkylsulphonylamino;
• R31 and R33 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, cyclopropyl, cyclobutyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulphinyl, ethylsulphinyl, mesyl, ethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulphamoyl, N-ethylsulphamoyl, N,N-dimethylsulphamoyl, N,N-diethylsulphamoyl or N-methyl-N-ethylsulphamoyl;
• or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof.