PHARMACEUTICAL COMPOUNDS

摘要

Fused pyrimidines of formula (1); wherein A represents a thiophene or a furan ring; n is 1 or 2; R¹ is a group of formula (); wherein m is 0 or 1; R³⁰ is H or C₁-C₆ alkyl; R⁴ and R⁵ form, together with the N atom to which they are attached a 5- or 6- membered saturated N-containing heterocyclic group which includes 0 or 1 additional heteroatoms selected from N, S and O, which may be fused to a benzene ring and which is unsubstituted or substituted; or one of R⁴ and R⁵ is alkyl and the other is a 5- Or 6-membered saturated N-containing heterocyclic group as defined above; R² is selected from a) formula (3) wherein R⁶ and R⁷ form, together with the nitrogen atom to which they are attached, a morpholine, thiomorpholine, piperidine, piperazine, oxazepane, or thiazepane group which is unsubstituted or substituted; and b) formula (4) wherein Y is a C₂-C₄ alkylene chain which contains, between constituent carbon atoms of the chain and/or at one or both ends of the chain, 1 or 2 heteroatoms selected from O, N and S, and which is unsubstituted or substituted; and R³ is selected from: (a) a group of the following formula: (5) 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)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 group comprising 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; provided that R³ is not an indole group or an indazole group, which group is unsubstituted or substituted; and the pharmaceutically acceptable salt thereof have activity as inhibitors of P13K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with P13 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.