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发明授权
CN101479276B 药用化合物 有权

药用化合物
摘要：
式(I)稠合的嘧啶：其中A代表噻吩或呋喃环；n是0、1或2；R1是下式基团：其中m是0或1；R30是H或C1-C6烷基；R4和R5与它们连接的N原子一起形成5-或6-元饱和的含N杂环基，该杂环基包含0或1个选自N、S和O的另外的杂原子，其可稠合至苯环并且是未取代的或取代的；或R4和R5之一是烷基和另一个是如上定义的5-或6-元饱和的含N杂环基或由如上定义的5-或6-元饱和的含N杂环基取代的烷基；R2是含1、2、3或4个环氮原子和1、2或3个选自O、N和S的另外的杂原子的杂芳基，该基团是单环或双环的并且是未取代的或取代的；和R3选自：(a)下式基团：其中B是未取代的或取代的苯基环和Z选自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、-RC(O)N(R)2、CN、卤素和-NO2，其中每一个R独立选自H、C1-C6烷基、C3-C10环烷基和5-12元芳基或杂芳基，所述基团是未取代的或取代的，m是1或2和q是0、1或2；(b)含1、2、3或4个环氮原子和0、1或2个选自O和S的另外的杂原子的杂芳基，该基团是单环或双环的并且是未取代的或取代的；和(c)包含未取代的或取代的和稠合至如上定义的杂芳基的苯环的基团；和其药学上可接受的盐具有如PBK抑制剂的活性，并且因此可用于治疗由与PI3激酶相关的异常的细胞生长、功能或行为所引起的疾病和紊乱，诸如癌症、免疫紊乱、心血管疾病、病毒性感染、炎症、代谢/内分泌紊乱和神经紊乱。也描述合成所述化合物的方法。
摘要（英）：

The invention provides fused pyrimidines of formula (I), wherein A represents a thiophene or furan ring; n is 0, 1 or 2; R1 is a group of the following 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 or an alkyl group which is substituted by a 5- or 6-membered saturated N-containing heterocyclic group as defined above; R2 is a heteroaryl group which contains I5 2, 3 or 4 ring nitrogen atoms and 0,1 or 2 additional heteroatoms selected from O, N and S, which group is monocyclic or bicyclic and which is unsubstituted or substituted; 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; (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. The pharmaceutically acceptable salt thereof have activity as inhibitors of PBK and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behavior associated with PI3 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.

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