公开(公告)号：US20090270427A1

公开(公告)日：2009-10-29

申请号：US12433388

申请日：2009-04-30

申请人： Peter Martin FISHER ,  Michael JARMAN ,  Edward MCDONALD ,  Bernard NUTLEY ,  Florence RAYNAUD ,  Stuart WILSON ,  Paul WORKMAN

发明人： Peter Martin FISHER ,  Michael JARMAN ,  Edward MCDONALD ,  Bernard NUTLEY ,  Florence RAYNAUD ,  Stuart WILSON ,  Paul WORKMAN

IPC分类号： A61K31/52 ,  C07D473/16 ,  A61P35/00 ,  C12N9/99

CPC分类号： C07D473/16

摘要： The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is methyl, ethyl or isopropyl, and the other is H; R3 and R4 are each independently H, branched or unbranched C1-C6 alkyl, or aryl, and wherein at least one of R3 and R4 is other than H; R5 is a branched or unbranched C1-C5 alkyl group or a C1-C6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R6, R7, R8 and R9 are each independently H, halogen, NO2, OH, OMe, CN, NH2, COOH, CONH2, or SO2NH2. A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, CNS disorders, diabetes, stroke, alopecia or neurodegenerative disorders.

摘要翻译： 本发明涉及式1化合物或其药学上可接受的盐，其中R 1和R 2之一是甲基，乙基或异丙基，另一个是H; R 3和R 4各自独立地为H，支链或非支链的C 1 -C 6烷基或芳基，并且其中R 3和R 4中的至少一个不是H; R5是支链或非支链C 1 -C 5烷基或C 1 -C 6环烷基，其各自可以任选被一个或多个OH基取代; R6，R7，R8和R9各自独立地为H，卤素，NO2，OH，OMe，CN，NH2，COOH，CONH2或SO2NH2。 本发明的另一方面涉及包含式1化合物的药物组合物，以及所述化合物在治疗增殖性疾病，病毒性疾病，中枢神经系统疾病，糖尿病，中风，脱发或神经变性疾病中的用途。

公开(公告)号：US20050107367A1

公开(公告)日：2005-05-19

申请号：US10486811

申请日：2002-08-14

申请人： Niall Martin ,  Graeme Cameron Smith ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  Laurent Rigoreau ,  David Newell ,  Hilary Calvert ,  Nicola Curtin ,  Paul Workman ,  Florence Raynaud ,  Bernard Nutley

发明人： Niall Martin ,  Graeme Cameron Smith ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  Laurent Rigoreau ,  David Newell ,  Hilary Calvert ,  Nicola Curtin ,  Paul Workman ,  Florence Raynaud ,  Bernard Nutley

IPC分类号： C12N9/99 ,  A61K31/5377 ,  A61P31/12 ,  A61P35/00 ,  A61P43/00 ,  C07D335/02 ,  C07D409/10 ,  A61K31/541 ,  A61K31/496 ,  C07D413/04 ,  C07D417/04 ,  C07D49/04

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，

公开(公告)号：US20050009846A1

公开(公告)日：2005-01-13

申请号：US10742237

申请日：2003-12-18

申请人： Peter Fischer ,  Mike Jarman ,  Ted McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

发明人： Peter Fischer ,  Mike Jarman ,  Ted McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

IPC分类号： A61K31/52 ,  A61P17/06 ,  A61P25/28 ,  A61P31/12 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D473/16 ,  C07D473/14

CPC分类号： C07D473/16

摘要： The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R2 is 2-hydroxymethylpyrrolidin-1-yl, or NHCH(R4)CH(R3)OH, wherein R3 is hydrogen or methyl and R4 is methyl, ethyl or isopropyl; R6 is 3-nitrophenylamino, 3,4-dimethoxybenzylamino, 3-iodobenzyl-amino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and or viral disorders.

摘要翻译： 本发明涉及式I化合物或其药学上可接受的盐，其中R2是2-羟甲基吡咯烷-1-基或NHCH（R4）CH（R3）OH，其中R3是氢或甲基，R4是甲基，乙基或 异丙基 R6是3-硝基苯基氨基，3,4-二甲氧基苄基氨基，3-碘苄基 - 氨基，吡啶-2-基 - 甲基氨基，吡啶-4-基 - 甲基氨基或茚满-5-氨基; R9是异丙基或环戊基。 在另一方面，本发明涉及包含所述化合物的药物组合物及其在治疗抗增生性疾病和/或病毒性疾病中的用途。

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 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：US08846696B2

公开(公告)日：2014-09-30

申请号：US12489663

申请日：2009-06-23

申请人： Peter Martin Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

发明人： Peter Martin Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

IPC分类号： A61K31/52 ,  C07D473/16

CPC分类号： C07D473/16 ,  A61K31/52 ,  Y02A50/411

摘要： The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is methyl, ethyl or isopropyl, and the other is H; R3 and R4 are each independently H, branched or unbranched C1-C6 alkyl, or aryl, and wherein at least one of R3 and R4 is other than H; R5 is a branched or unbranched C1-C5 alkyl group or a C1-C6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R6, R7, R8 and R9 are each independently H, halogen, NO2, OH, OMe, CN, NH2, COOH, CONH2, or SO2NH2. A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, stroke, alopecia, CNS disorders, neurodegenerative disorders, or diabetes.

摘要翻译： 本发明涉及式1化合物或其药学上可接受的盐，其中R 1和R 2之一是甲基，乙基或异丙基，另一个是H; R 3和R 4各自独立地为H，支链或非支链的C 1 -C 6烷基或芳基，并且其中R 3和R 4中的至少一个不是H; R5是支链或非支链C 1 -C 5烷基或C 1 -C 6环烷基，其各自可以任选被一个或多个OH基取代; R6，R7，R8和R9各自独立地为H，卤素，NO2，OH，OMe，CN，NH2，COOH，CONH2或SO2NH2。 本发明的另一方面涉及包含式1化合物的药物组合物，以及所述化合物在治疗增殖性疾病，病毒性疾病，中风，脱发，中枢神经系统疾病，神经变性疾病或糖尿病中的用途。

公开(公告)号：US07544689B2

公开(公告)日：2009-06-09

申请号：US11238533

申请日：2005-09-28

申请人： Peter Martin Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

发明人： Peter Martin Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

IPC分类号： C07D473/16 ,  A61K31/52 ,  A61P35/00 ,  A61P3/10 ,  A61P31/20 ,  A61P31/14 ,  A61P17/06 ,  A61P35/02 ,  A61P25/28

CPC分类号： C07D473/16

摘要： The present invention relates to compounds of formula I or pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is methyl, ethyl or isopropyl, and the other is H; R3 and R4 are each independently H, branched or un branched C1-C6 alkyl, or aryl, and wherein at least one of R3 and R4 is other than H; R5 is a branched or unbranched C1-C5 alkyl group or a C1-C6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R6, R7, R8 and R9 are each independently H, halogen, NO2, OH, OMe, CN, NH2, COOH, CONH2, or SO2NH2. A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, CNS disorders, diabetes, stroke, alopecia or neurodegenerative disorders.

摘要翻译： 本发明涉及式I化合物或其药学上可接受的盐，其中R 1和R 2之一是甲基，乙基或异丙基，另一个是H; R 3和R 4各自独立地为H，支链或非支链C 1 -C 6烷基或芳基，并且其中R 3和R 4中的至少一个不是H; R5是支链或非支链C 1 -C 5烷基或C 1 -C 6环烷基，其各自可以任选被一个或多个OH基取代; R6，R7，R8和R9各自独立地为H，卤素，NO2，OH，OMe，CN，NH2，COOH，CONH2或SO2NH2。 本发明的另一方面涉及包含式1化合物的药物组合物，以及所述化合物在治疗增殖性疾病，病毒性疾病，中枢神经系统疾病，糖尿病，中风，脱发或神经变性疾病中的用途。

公开(公告)号：US20050256142A1

公开(公告)日：2005-11-17

申请号：US11033692

申请日：2005-01-11

申请人： Peter Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

发明人： Peter Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

IPC分类号： A61K31/52 ,  A61P3/10 ,  A61P9/00 ,  A61P17/06 ,  A61P17/14 ,  A61P25/28 ,  A61P31/12 ,  A61P35/00 ,  C07D473/16 ,  C07D473/12

CPC分类号： C07D473/16 ,  A61K31/52 ,  Y02A50/411

摘要： The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is methyl, ethyl or isopropyl, and the other is H; R3 and R4 are each independently H, branched or unbranched C1-C6 alkyl, or aryl, and wherein at least one of R3 and R4 is other than H; R5 is a branched or unbranched C1-C5 alkyl group or a C1-C6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R6, R7, R8 and R9 are each independently H, halogen, NO2, OH, OMe, CN, NH2, COOH, CONH2, or SO2NH2. A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, CNS disorders, diabetes, stroke, alopecia or neurodegenerative disorders.

摘要翻译： 本发明涉及式1化合物或其药学上可接受的盐，其中R 1和R 2之一是甲基，乙基或异丙基，另一个是H; R 3和R 4各自独立地为H，支链或非支链C 1 -C 6烷基或芳基 并且其中R 3和R 4中的至少一个不是H; R 5是支链或非支链C 1 -C 5烷基或C 1 -C 3亚烷基 其中每一个可以任选地被一个或多个OH基团取代; R 6，R 7，R 8和R 9各自独立地为H，卤素，NO 3， 2，OH，OMe，CN，NH 2，COOH，CONH 2或SO 2 NH 2， / SUB>。 本发明的另一方面涉及包含式1化合物的药物组合物，以及所述化合物在治疗增殖性疾病，病毒性疾病，中枢神经系统疾病，糖尿病，中风，脱发或神经变性疾病中的用途。

公开(公告)号：US20090325983A1

公开(公告)日：2009-12-31

申请号：US12489663

申请日：2009-06-23

申请人： Peter Martin FISCHER ,  Michael JARMAN ,  Edward MCDONALD ,  Bernard NUTLEY ,  Florence RAYNAUD ,  Stuart WILSON ,  Paul WORKMAN

发明人： Peter Martin FISCHER ,  Michael JARMAN ,  Edward MCDONALD ,  Bernard NUTLEY ,  Florence RAYNAUD ,  Stuart WILSON ,  Paul WORKMAN

IPC分类号： A61K31/52 ,  C07D473/16 ,  C12Q1/48

CPC分类号： C07D473/16 ,  A61K31/52 ,  Y02A50/411

摘要： The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is methyl, ethyl or isopropyl, and the other is H; R3 and R4 are each independently H, branched or unbranched C1-C6 alkyl, or aryl, and wherein at least one of R3 and R4 is other than H; R5 is a branched or unbranched C1-C5 alkyl group or a C1-C6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R6, R7, R8 and R9 are each independently H, halogen, NO2, OH, OMe, CN, NH2, COOH, CONH2, or SO2NH2. A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, stroke, alopecia, CNS disorders, neurodegenerative disorders, or diabetes.

摘要翻译： 本发明涉及式1化合物或其药学上可接受的盐，其中R 1和R 2之一是甲基，乙基或异丙基，另一个是H; R 3和R 4各自独立地为H，支链或非支链的C 1 -C 6烷基或芳基，并且其中R 3和R 4中的至少一个不是H; R5是支链或非支链C 1 -C 5烷基或C 1 -C 6环烷基，其各自可以任选被一个或多个OH基取代; R6，R7，R8和R9各自独立地为H，卤素，NO2，OH，OMe，CN，NH2，COOH，CONH2或SO2NH2。 本发明的另一方面涉及包含式1化合物的药物组合物，以及所述化合物在治疗增殖性疾病，病毒性疾病，中风，脱发，中枢神经系统疾病，神经变性疾病或糖尿病中的用途。

公开(公告)号：US07612079B2

公开(公告)日：2009-11-03

申请号：US10742237

申请日：2003-12-18

申请人： Peter Martin Fischer ,  Mike Jarman ,  Ted McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

发明人： Peter Martin Fischer ,  Mike Jarman ,  Ted McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

IPC分类号： C07D473/16 ,  A61K31/52 ,  A61P35/00 ,  C07C215/08 ,  A61P17/06 ,  A61P35/02

CPC分类号： C07D473/16

摘要： The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R2 is 2-hydroxymethylpyrrolidin-1-yl, or NHCH(R4)CH(R3)OH, wherein R3 is hydrogen or methyl and R4 is methyl, ethyl or isopropyl; R6 is 3-nitrophenylamino, 3,4-dimethoxybenzylamino, 3-iodobenzyl-amino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and or viral disorders.

摘要翻译： 本发明涉及式I化合物或其药学上可接受的盐，其中R2是2-羟甲基吡咯烷-1-基或NHCH（R4）CH（R3）OH，其中R3是氢或甲基，R4是甲基，乙基或 异丙基 R6是3-硝基苯基氨基，3,4-二甲氧基苄基氨基，3-碘苄基 - 氨基，吡啶-2-基 - 甲基氨基，吡啶-4-基 - 甲基氨基或茚满-5-氨基; R9是异丙基或环戊基。 在另一方面，本发明涉及包含所述化合物的药物组合物及其在治疗抗增生性疾病和/或病毒性疾病中的用途。

公开(公告)号：US07582642B2

公开(公告)日：2009-09-01

申请号：US11033692

申请日：2005-01-11

申请人： Peter Martin Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

发明人： Peter Martin Fischer ,  Michael Jarman ,  Edward McDonald ,  Bernard Nutley ,  Florence Raynaud ,  Stuart Wilson ,  Paul Workman

IPC分类号： C07D473/16 ,  A61K31/52 ,  A61P35/00 ,  A61P31/14 ,  A61P31/20 ,  C07D473/40

CPC分类号： C07D473/16 ,  A61K31/52 ,  Y02A50/411

摘要： The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is methyl, ethyl or isopropyl, and the other is H; R3 and R4 are each independently H, branched or unbranched C1-C6 alkyl, or aryl, and wherein at least one of R3 and R4 is other than H; R5 is a branched or unbranched C1-C5 alkyl group or a C1-C6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R6, R7, R8 and R9 are each independently H, halogen, NO2, OH, OMe, CN, NH2, COOH, CONH2, or SO2NH2. A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, stroke, alopecia, CNS disorders, neurodegenerative disorders, or diabetes.

摘要翻译： 本发明涉及式1化合物或其药学上可接受的盐，其中R 1和R 2之一是甲基，乙基或异丙基，另一个是H; R 3和R 4各自独立地为H，支链或非支链的C 1 -C 6烷基或芳基，并且其中R 3和R 4中的至少一个不是H; R5是支链或非支链C 1 -C 5烷基或C 1 -C 6环烷基，其各自可以任选被一个或多个OH基取代; R6，R7，R8和R9各自独立地为H，卤素，NO2，OH，OMe，CN，NH2，COOH，CONH2或SO2NH2。 本发明的另一方面涉及包含式1化合物的药物组合物，以及所述化合物在治疗增殖性疾病，病毒性疾病，中风，脱发，中枢神经系统疾病，神经变性疾病或糖尿病中的用途。