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公开(公告)号:US20070238729A1
公开(公告)日:2007-10-11
申请号:US11758332
申请日:2007-06-05
申请人: Niall Martin , Graeme Smith , Roger Griffin , Bernard Golding , Ian Hardcastle , David Newell , Hilary Calvert , Nicola Curtin , Laurent Rigoreau , Xiao-ling Cockcroft , Vincent Junior Loh , Paul Workman , Florence Raynaud , Bernard Nutley
发明人: Niall Martin , Graeme Smith , Roger Griffin , Bernard Golding , Ian Hardcastle , David Newell , Hilary Calvert , Nicola Curtin , Laurent Rigoreau , Xiao-ling Cockcroft , Vincent Junior Loh , Paul Workman , Florence Raynaud , Bernard Nutley
IPC分类号: A61K31/351 , A61K31/519 , A61K31/5377 , A61P35/00
CPC分类号: C07D417/04 , C07D309/38 , C07D311/22 , C07D311/92 , C07D471/04
摘要: The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R1 and R2 are independently hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CR4 and O, O and CR′4 and NR″4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R3 and R4 or R′4 is an optionally substituted C3-20 heteroaryl or C5-20 aryl group, and the other of R3 and R4 or R′4 is H, or R3 and R4 or R″4 together are -A-B—, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.
摘要翻译: 本发明涉及式(I)化合物及其异构体,盐,溶剂合物,化学保护形式及其前药在制备用于抑制DNA-PK活性的药物中的用途,其中R 1, R 2和R 2各自独立地为氢,任选取代的C 1-7 - 烷基,C 3-20杂环基或C 或者可以与它们所连接的氮原子一起形成具有4至8个环原子的任选取代的杂环; X和Y选自CR 4和O,O和CR'4和NR“4和N,其中不饱和键处于 R 2中的一个是R 3,R 4,R 4和R 4中的一个是任选取代的C 3 -20个杂芳基或C 5-20-20芳基,R 3和R 4中的另一个或R' > 4 SUP>是H,或R 3和R 4或R“4”一起是-AB-,它们共同表示 稠合的任选取代的芳环。 与PI3-激酶和/或ATM相比,化合物还选择性地抑制DNA-PK的活性。