公开(公告)号：US07674823B2

公开(公告)日：2010-03-09

申请号：US11758332

申请日：2007-06-05

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Murray Smith ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Laurent Jean Martin Rigoreau ,  Xiao-ling Fan Cockcroft ,  Vincent Junior Ming-lai Loh ,  Paul Workman ,  Florence Irene Raynaud ,  Bernard Paul Nutley

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Murray Smith ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Laurent Jean Martin Rigoreau ,  Xiao-ling Fan Cockcroft ,  Vincent Junior Ming-lai Loh ,  Paul Workman ,  Florence Irene Raynaud ,  Bernard Paul Nutley

IPC分类号： A61K31/351

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R1和R2独立地为氢 ，任选取代的C 1-7烷基，C 3-20杂环基或C 5-20芳基，或者可以与它们所连接的氮原子一起形成任选取代的具有4-8个环的杂环 原子 X和Y选自CR4和O，O和CR'4和NR "4和N，其中不饱和键在环中的适当位置，并且其中R3和R4或R'4之一是任选取代的C3 -20杂芳基或C5-20芳基，R3和R4或R'4中的另一个为H，或R3和R4或R“4一​​起为-A-B-，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。

公开(公告)号：US07226918B2

公开(公告)日：2007-06-05

申请号：US10486816

申请日：2002-08-14

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Murray Smith ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Laurent Jean Martin Rigoreau ,  Xiao-ling Fan Cockcroft ,  Vincent Junior Ming-lai Loh ,  Paul Workman ,  Florence Irene Raynaud ,  Bernard Paul Nutley

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Murray Smith ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Laurent Jean Martin Rigoreau ,  Xiao-ling Fan Cockcroft ,  Vincent Junior Ming-lai Loh ,  Paul Workman ,  Florence Irene Raynaud ,  Bernard Paul Nutley

IPC分类号： A61K31/353 ,  A61K31/5377 ,  C07D265/30 ,  C07D311/58

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4-8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 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。

公开(公告)号：US07105518B2

公开(公告)日：2006-09-12

申请号：US10486811

申请日：2002-08-14

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Murray Smith ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  Laurent Jean Martin Rigoreau ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Paul Workman ,  Florence Irene Raynaud ,  Bernard Paul Nutley

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Murray Smith ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  Laurent Jean Martin Rigoreau ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Paul Workman ,  Florence Irene Raynaud ,  Bernard Paul Nutley

IPC分类号： A61K31/382 ,  C07D335/02 ,  A61N5/00 ,  A61K31/5355 ,  C07D413/04

CPC分类号： C07D335/02

摘要： The present invention provides compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein R1 and R2 are independently hydrogen, an option ally 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; and R3 is an optionally substituted C3-20 heterocyclyl or C5-20 aryl group, and their use as pharmaceuticals, particularly in treating diseases which are retroviral mediated or ameliorated by the inhibition of DNA-PK,

摘要翻译： 本发明提供式（I）化合物及其异构体，盐，溶剂化物，化学保护形式及其前药，其中R 1和R 2独立地为氢， 选择性地取代C 1-7烷基，C 3-20杂环基或C 5-20-20芳基，或可一起形成 与它们所连接的氮原子一起形成具有4-8个环原子的任选取代的杂环; 并且R 3是任选取代的C 3-20杂环基或C 5-20芳基，并且它们作为药物的用途，特别是在治疗 通过抑制DNA-PK介导或改善的逆转录病毒的疾病，