2-Arylamino-pyrimidines for the treatment of gsk3-related disorders

Use of a compound of formula (I)

• 14
• wherein:
• Ring A is imidazo[1,2a]pyrid-3-yl or pyrazolo[2,3a]pyrid-3-yl;
• R2 is attached to a ring carbon and is selected from halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 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, 1, or 2, C1-6alkoxycarbonyl, N-(C1-6alkyl)sulphamoyl, N,N-(C1-6alkyl)2sulphamoyl, phenyl, heterocyclic group, phenylthio and, (heterocyclic group)thio;
• wherein any C1-6alkyl, C2-6alkenyl, C2-6alkynyl, phenyl or heterocyclic group may be optionally substituted on carbon by one or more G;
• and wherein if said heterocyclic group contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from Q;
• m is 0, 1, 2, 3, 4 or 5;
• wherein the values of R2 may be the same or different;
• R1 is halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-3alkyl, C2-3alkenyl, C2-3alkynyl, C1-3alkoxy, C1-3alkanoyl, N-(C1-3alkyl)amino, N,N-(C1-2alkyl)2amino, C1-3alkanoylamino, N-(C1-3alkyl)carbamoyl, N,N-(C1-2alkyl)2carbamoyl, C1-3alkylS(O)a wherein a is 0, 1 or 2, N-(C1-3alkyl)sulphamoyl or N,N-(C1-3alkyl)2sulphamoyl;
• wherein any C1-2alkyl, C1-3alkyl, C2-3alkenyl or C2-3alkynyl may be optionally substituted on carbon by one or more J;
• n is 0, 1 or 2, wherein the values of R1 may be the same or different;
• Ring B is phenyl or phenyl fused to a C5-7cycloalkyl ring;
• R3 is halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl or C1-6alkoxy,
• p is 0, 1 2, 3 or 4;
• wherein the values of R3 may be the same or different;
• R4 is a group A-E-;
• wherein
• A is selected from hydrogen, C1-6alkyl, phenyl, a heterocyclic group, C3-8cycloalkyl, phenylC1-6alkyl, (heterocyclic group)C1-6alkyl or C3-8cycloalkylC1-6cycloalkyl;
• which C1-6alkyl, phenyl, a heterocyclic group, C3-8cycloalkyl, phenylC1-6alkyl, (heterocyclic group)C1-6alkyl or C3-8cycloalkylC1-6cycloalkyl may be optionally substituted on carbon by one or more D;
• and wherein if said heterocyclic group contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R;
• E is a direct bond or —O—, —C(O)—, —OC(O)—, —C(O)O—, —N(Ra)C(O)—, —C(O)N(Ra)—, —N(Ra)—, —S(O)r—, —SO2N(Ra)— or —N(Ra)SO2—;
• wherein Ra is hydrogen or C1-6alkyl optionally substituted by one or more D and r is 0, 1 or 2;
• D is independently selected from oxo, halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, 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, C1alkanoylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, C1 alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, C1-6alkoxycarbonylamino, benzyloxycarbonylamino, N-(C1-6alkyl)sulphamoyl and N,N-(C1-6 alkyl)2sulphamoyl;
• wherein any C1-6alkyl, C2-6alkenyl, C2-6alkynyl or phenyl may be optionally substituted on carbon by one or more K;
• q is 0, 1 or 2;
• wherein the values of R4 maybe the same or different;
• and wherein p+q≦5;
• G, J and K are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, 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 and N-methyl-N-ethylsulphamoyl;
• and
• Q and R 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 thereof in the manufacturing of a medicament for the treatment and/or prophylaxis of conditions associated with glycogen synthase kinase-3 inhibition.