Pyrimidine compounds

A pyrimidine derivative of the formula (I):

• 33
• wherein:
• Q1 and Q2 are independently selected from aryl or carbon linked heteroaryl;
• and one of Q1 and Q2 or both Q1 and Q2 is substituted on a ring carbon by one group selected from sulphamoyl, N—(C1-4alkyl)sulphamoyl (optionally substituted by halo or hydroxy), N,N-di-(C1-4alkyl)sulphamoyl (optionally substituted by halo or hydroxy), C1-4alkylsulphonyl (optionally substituted by halo or hydroxy) or a substituent of the formula (Ia) or (Ia′):
• 34
• wherein:
• Y is —NHS(O)2—, —S(O)2NH— or —S(O)2—;
• Z is RaO—, RbRcN—, RdS—, ReRfNNRg—, C3-8cycloalkyl, phenyl or a heterocyclic group;
• wherein said phenyl, C3-8cycloalkyl or heterocyclic group are optionally substituted on a rig carbon by one or more groups selected from Rh;
• and wherein if said heterocyclic group contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from Ri;
• Ra, Rb, Rc, Rd, Re, Rf and Rg are independently selected from hydrogen, C1-4alkyl, C2-4alkenyl, phenyl, heterocyclic group and C3-8cycloalkyl;
• wherein said C1-4alkyl, C2-4alkenyl and C3-8cycloalkyl are optionally substituted by one or more groups selected from Rj;
• n is 0 or 1;
• m is 1, 2 or 3, in addition m may be 0 when Z is C3-8cycloalkyl, phenyl or a heterocyclic group;
• Q3 is a nitrogen linked heterocycle;
• wherein said heterocycle is optionally substituted on a ring carbon by one or more groups selected from R1;
• and wherein if said heterocyclic group contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from Rm
• G is —O—, —S— or —NR2—;
• R2 is selected from hydrogen, C1-6alkyl, C3-6alkenyl and C3-6alkynyl;
• wherein said C1-6alkyl, C3-6alkenyl and C3-6alkynyl are optionally substituted by one or more groups selected from Rn;
• R1 is selected from hydrogen, halo, hydroxy, nitro, amino, N—(C1-3alkyl)amino, N,N-di-(C1-3alkyl)amino, cyano, trifluoromethyl, trichloromethyl, C1-3alkyl [optionally substituted by 1 or 2 substituents independently selected from halo, cyano, amino, N—(C1-1alkyl)amino, N,N-di-(C1-3alkyl)amino, hydroxy and trifluoromethyl], C3-5alkenyl [optionally substituted by up to three halo substituents, or by one trifluoromethyl substituent], C3-5alkynyl, C1-3alkoxy, mercapto, C1-3alkylsulphanyl, carboxy and C1-3alkoxycarbonyl;
• Q1 is optionally substituted on a ring carbon by one to four substituents independently selected from halo, mercapto, nitro, formyl, formamido, carboxy, cyano, amino, ureido, carbamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl [wherein said C1-4alkyl, C2-4alkenyl and C2-4alkynyl are optionally substituted by one or more groups selected from Ro], C1-4alkanoyl, C1-4alkoxycarbonyl, heterocyclic group, C1-4alkylS(O)a wherein a is 0 or 1 [optionally substituted by hydroxy], N′—(C1-4alkyl)ureido, N′,N′-di-(C1-4alkyl)ureido, N′—(C1-4alkyl)-N—(C1-4alkyl)ureido, N′,N′-di-(C1-4alkyl)-N—(C1-4alkyl)ureido, N—C1-4alkylamino, N,N-di-(C1-4alkyl)amino, N—C1-4alkylcarbamoyl, N,N-di-(C1-4alkyl)carbamoyl and C1-4alkanoylamino;
• and also independently, or in addition to, the above substituents, Q1 may be optionally substituted by one to two substituents independently selected from aryl, C3-8cycloalkyl and a heterocyclic group;
• wherein said aryl, C3-8cycloalkyl or heterocyclic group may be optionally substituted on a ring carbon by one or more groups selected from Rp;
• and wherein if said heterocyclic group contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from Rq;
• and also independently, or in addition to, the above substituents, Q1 may be optionally substituted by one C1-4alkoxy or by one hydroxy substituent;
• Q2 is optionally substituted on a ring carbon by one to four substituents independently selected from halo, hydroxy, mercapto, nitro, formyl, formamido, carboxy, cyano, amino, ureido, carbamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy [wherein said C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C1-4alkoxy are optionally substituted by one or more groups selected from R1], C1-4alkanoyl, C1-4alkoxycarbonyl, heterocyclic group, C1-4alkylS(O)a wherein a is 0 or 1 [optionally substituted by hydroxy], N′—(C1-4alkyl)ureido, N′,N′-di-(C1-4alkyl)ureido, N′—(C1-4alkyl)-N—(C1-4alkyl)ureido, N′,N′,-di-(C1-4alkyl)-N—(C1-4alkyl)ureido, N—C1-4alkylamino, N,N-di-(C1-4alkyl)amino, N—C1-4alkylcarbamoyl, N,N-di-(C1-4alkyl)carbamoyl, C1-4alkenyloxy, C2-4alkynyloxy and C1-4alkanoylamino;
• and also independently, or in addition to, the above substituents, Q2 may be optionally substituted by one to two substituents independently selected from aryl, C3-8cycloalkyl or a heterocyclic group;
• wherein said aryl, C3-8cycloalkyl or heterocyclic group may be optionally substituted on a ring carbon by one or more groups selected from Rs;
• and wherein if said heterocyclic group contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from Rt;
• Rj, Rn, Ro and Rr are independently selected from hydroxy, halo, amino, cyano, formyl, formamido, carboxy, nitro, mercapto, carbamoyl, sulphamoyl, N—C1-4alkylamino, N,N-di-(C1-4alkyl)amino, C1-4alkanoyl, C1-4alkanoyloxy, C1-4alkoxy, C1-4alkoxycarbonyl, N—C1-4alkylcarbamoyl, N,N-di-(C1-4alkyl)carbamoyl, C1-4alkanoylamino, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkylsulphonylamino, N—(C1-4alkyl)sulphamoyl, N—(C1-4alkyl)2sulphamoyl, N—(C1-4alkyl)carbamoyl, N—(C1-4alkyl)2carbamoyl, phenyl, phenylthio, phenoxy, C3-8cycloalkyl and a heterocyclic group;
• wherein said phenyl, phenylthio, phenoxy, C3-8cycloalkyl or heterocyclic group may be optionally substituted on a ring carbon by one or more groups selected from Ru;
• and wherein if said heterocyclic group contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from Rv.
• Rh, Rk, Rp Rs and Ru are independently selected from hydroxy, halo, amino, cyano, formyl, formamido, carboxy, nitro, mercapto, carbamoyl, sulphamoyl, C1-4alkyl [optionally substituted by one or more groups selected from halo, cyano, amino, N—C1-4alkylamino, N,N-di-(C1-4alkyl)amino or hydroxy], C2-4alkenyl [optionally substituted by one or more groups selected from halo], C2-4alkynyl, N—C1-4alkylamino, N,N-di-(C1-4alkyl)amino, C1-4alkanoyl, C1-4alkanoyloxy, C1-4alkoxy [optionally substituted by one or more groups selected from halo], C1-4alkoxycarbonyl, N—C1-4alkylcarbamoyl, N,N-di-(C1-4alkyl)carbamoyl, C1-4alkanoylamino, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkylsulphonylamino, N—(C1-4alkyl)sulphamoyl, N—(C1-4alkyl)2sulphamoyl, phenyl, C3-8cycloalkyl and a heterocyclic group;
• and
• Ri, Rq, Rt and Rv are independently selected from C1-4alkyl, C1-4alkanoyl, C1-4alkylsulphonyl, C1-4alkoxycarbonyl, carbamoyl, N—(C1-4alkyl)carbamoyl, N,N—(C1-4alkyl)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
• or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof.