| 主权项 |
1. A compound which is a fused pyrimidine of formula (Ia): wherein X is O or S; R1 is a group of formula: R2 is H, halo or C1-C6 alkyl R4 and R5 form, together with the N atom to which they are attached, a group selected from piperazine, piperidine, pyrrolidine, oxazolidinone, diazepan and 2,5-diaza-bicyclo[2,2,1]-heptane, which group is unsubstituted or substituted by -[(alk)q-NR]r—S(O)2-(alk)q-Z or —C(O)-(alk)q-S(O)2Z wherein Z is R10 or —NR11R12, or by unsubstituted C1-C6 alkyl, hydroxyl-C1-C6 alkyl, oxo (═O), -(alk)q-OR, —C(O)—C(R′)2—N(R)2, —C(R)2—C(O)—N(R)2, —C(O)—(NR)q-(alk)q-OR, —C(O)-cyclyl, —C(O)R, —C(O)OR, —C(O)-Tet or —NR13R14; or one of R4 and R5 is C1-C6 alkyl, -(alk)q-Heterocyclyl or -(alk)q-OR and the other is a piperazine, piperidine, pyrrolidine, sulphonylpyran or -(alk)q-Heterocyclyl group, wherein said piperazine, piperidine, pyrrolidine, sulphonylpyran or Heterocyclyl is unsubstituted or substituted by C1-C6 alkyl, -(alk)q-OR or —S(O)2R10; R is H or C1-C6 alkyl which is unsubstituted; each R′ is, independently, H or C1-C6 alkyl which is unsubstituted, or the two groups R′ form, together with the C atom to which they are attached, a cyclyl group; R10 is H, cyclyl, C1-C6 alkyl which is unsubstituted or CF3; R11 and R12 are each independently selected from H, C1-C6 alkyl which is unsubstituted and -(alk)q—OR, or R11 and R12 together form, with the N atom to which they are attached, a 5- or 6-membered saturated N-containing heterocyclic group containing 0 or 1 additional heteroatoms selected from O, N and S; R13 and R14 are each independently selected from C1-C6 alkyl, —S(O)2R10, and -(alk)q-OR; Tet is a tetrahydrofuranyl or tetrahydropyranyl group, which group is unsubstituted or substituted; Heterocyclyl is a 5- or 6-membered saturated N-containing heterocyclic group containing 0 or 1 additional heteroatoms selected from O, N and S; Cyclyl is a C3-C6 cycloalkyl group; each q is independently 0 or 1; r is 0 or 1; alk is C1-C6 alkylene; and R3 is selected from:
(a) a group of the following formula: wherein B is a phenyl ring which is unsubstituted or substituted, and Z is selected from H, —OR, —SR, CH2OR, —CO2R, CF2OH, CH(CF3)OH, C(CF3)2OH, —(CH2)qOR, —(CH2)qNR2—C(O)N(R)2, —NR2, —NRC(O)R, —S(O)mN(R)2, —OC(O)R, OC(O)N(R)2, —NRS(O)mR, —NRC(O)N(R)2, CN, halogen and —NO2, wherein each R is independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl and a 5- to 12-membered aryl or heteroaryl group, the group being unsubstituted or substituted, m is 1 or 2 and q is 0, 1 or 2;(b) a heteroaryl group which contains 1, 2, 3 or 4 ring nitrogen atoms and 0, 1 or 2 additional heteroatoms selected from O and S, which group is monocyclic or bicyclic and which is unsubstituted or substituted; and(c) a benzene ring which is unsubstituted or substituted and which is fused to a heteroaryl group as defined above; or a pharmaceutically acceptable salt thereof; with the provisos that:
(i) when X in formula (Ia) is S, then R3 is other than an indole or 3-hydroxyphenyl group;(ii) when X in formula (Ib) is S, then R3 is other than an indole group;(iii) in formula (Ia) only, when X is S and R2 is H and R3 is indazol-4-yl, then R4 and R5 do not form: (i) piperazine which is unsubstituted or substituted by a group selected from methyl, —S(O)2Me, —S(O)2NMe2, -alk-OH, -alk-OMe, —S(O)2-alk-NMe2, and —S(O)2-alk-morpholino; or (ii) piperidine which is substituted by a group selected from —S(O)2Me, —C(O)—NR-(alk)q-OR, —NMe-S(O)2-Me, methyl, piperidine and —NR13R14 wherein one of R13 and R14 is -(alk)q-OR. |
