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公开(公告)号:US20050059663A1
公开(公告)日:2005-03-17
申请号:US10876080
申请日:2004-06-24
申请人: Niall Morrison Martin , Graeme Smith , Stephen Jackson , Vincent M Loh , Xiao-Ling Cockcroft , Ian Timothy Matthews , Keith Menear , Frank Kerrigan , Alan Ashworth
发明人: Niall Morrison Martin , Graeme Smith , Stephen Jackson , Vincent M Loh , Xiao-Ling Cockcroft , Ian Timothy Matthews , Keith Menear , Frank Kerrigan , Alan Ashworth
IPC分类号: A61K31/00 , C07D237/32 , C07D401/10 , C07D401/12 , C07D401/14 , C07D403/10 , C07D403/12 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/12 , C07D417/14 , C07D471/20 , C07D491/04 , C07D495/04 , C07D237/26 , A61K31/502 , C07D43/02
CPC分类号: A61K31/00 , C07D237/32 , C07D401/10 , C07D401/12 , C07D401/14 , C07D403/10 , C07D403/12 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/12 , C07D417/14 , C07D491/04 , C07D495/04
摘要: Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X═NRX then n is 1 or 2 and if X═CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.
摘要翻译: 式(I)的化合物:其中A和B一起表示任选取代的稠合芳环; X可以是NR X或CR X R Y; 如果X = NR X,那么n是1或2,如果X = CR X R Y,那么n是1; R X选自H,任选取代的C 1-20烷基,C 5-20芳基,C 3-20杂环基,酰氨基,硫代酰氨基,酯,酰基和磺酰基; R Y选自H,羟基,氨基; 或R X和R Y可以一起形成螺C 3-7环烷基或杂环基; R C1和R C2都是氢,或者当X是CR X R Y,R C1,R C2,R X和R Y时,与碳 它们所连接的原子可以形成任选取代的稠合芳环; 且R 1选自H和卤素。
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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。
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公开(公告)号:US20080081809A1
公开(公告)日:2008-04-03
申请号:US11842930
申请日:2007-08-21
申请人: Heather Duggan , Karine Malagu , Frederic Leroux , Niall Martin , Keith Menear , Graeme Smith
发明人: Heather Duggan , Karine Malagu , Frederic Leroux , Niall Martin , Keith Menear , Graeme Smith
IPC分类号: A61K31/5377 , A61P35/00 , C07D413/02 , C07D413/14
CPC分类号: A61K31/5377 , A61K31/565 , A61K45/06 , C07D413/14 , C07D471/04 , C07D475/08 , C07D475/10
摘要: There is provided a compound of formula I: , or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.
摘要翻译: 提供式I化合物或其药学上可接受的盐。 还提供了制备式1化合物的方法和式1化合物作为药物和用于治疗癌症的用途。
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公开(公告)号:US20060178361A1
公开(公告)日:2006-08-10
申请号:US11351052
申请日:2006-02-09
申请人: Marc Hummersone , Keith Menear , Laurent Rigoreau , Graeme Smith , Niall Martin , Roger Griffin
发明人: Marc Hummersone , Keith Menear , Laurent Rigoreau , Graeme Smith , Niall Martin , Roger Griffin
IPC分类号: A61K31/55 , A61K31/453 , C07D409/14
CPC分类号: C07D409/04 , C07D409/14
摘要: A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R1 and R2 together form, along with the nitrogen atom to which they are attached, an optionally substituted nitrogen containing heterocyclic ring having from 4 to 8 ring atoms; and R3 is selected from hydroxy and —NRN1RN2, where RN1 and RN2 are independently selected from hydrogen, optionally substituted C1-7 alkyl groups, optionally substituted C3-20 heterocyclyl groups and optionally substituted C5-20 aryl groups, or together form, along with the nitrogen atom to which they are attached, an optionally substituted nitrogen containing heterocyclic ring having from 4 to 8 ring atoms, and its use in inhibiting ATM.
摘要翻译: 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 2一起与氮原子一起形成 它们所连接的是具有4-8个环原子的任选取代的含氮杂环; R 3和R 3选自羟基和-NR N 1 N 2 N 2,其中R 11和R 10独立地选自氢, N 2独立地选自氢,任选取代的C 1-7烷基,任选取代的C 3-20杂环基和任选取代的C 5 -20个芳基,或者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含氮杂环,以及其在抑制ATM中的用途。
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公开(公告)号:US20070238731A1
公开(公告)日:2007-10-11
申请号:US11575606
申请日:2005-09-20
申请人: Graeme Smith , Niall Martin , Roger Griffin , Bernard Golding , Ian Hardcastle , Kappusamy Saravanan , David Newell , Hilary Calvert , Nicola Curtin , Keith Menear , Marc Hummersone
发明人: Graeme Smith , Niall Martin , Roger Griffin , Bernard Golding , Ian Hardcastle , Kappusamy Saravanan , David Newell , Hilary Calvert , Nicola Curtin , Keith Menear , Marc Hummersone
IPC分类号: A61K31/5355 , C07D413/14
CPC分类号: C07D413/14 , C07D409/04 , C07D409/14
摘要: A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R1 and R2 are independently selected from hydrogen, an optionally substituted C1-7 alkyl group, C3-20heterocyclyl 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; Q is —NH—C(═O)— or —O—; Y is an optionally substituted C1-5 alkylene group; X is selected from SR3 or NR4R5, wherein, R3 or R4 and R5 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R4 and R5 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; if Q is —O—, X is additionally selected from —C(═O)—NR6R7, wherein R6 and R7 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R6 and R7 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 if Q is —NH—C(═O)—, —Y—X may additionally be selected from C1-7 alkyl.
摘要翻译: 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,其中:R 1和R 2独立地选自氢,任选地 取代的C 1-7烷基,C 3-20杂环基或C 5-20-20芳基,或者可以一起形成 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; Q是-NH-C(-O) - 或-O-; Y是任选取代的C 1-5亚烷基; X选自SR 3或NR 4 R 5,其中,R 3或R 4 R 5和R 5独立地选自氢,任选取代的C 1-7 - 烷基,C 5-20芳基或C 3-20个杂环基或R 4和R 5可以一起与它们所连接的氮原子一起形成任选地 具有4至8个环原子的取代杂环; 如果Q是-O-,X另外选自-C(-O)-NR 6 R 7,其中R 6和R 独立地选自氢,任选取代的C 1-7 - 烷基,C 5-20-20芳基或C 3-20 或者R 6和R 7可以与它们所连接的氮原子一起形成任选取代的杂环,其具有4个 至8个环原子; 并且如果Q是-NH-C(-O) - ,-Y-X可另外选自C 1-7烷基。
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公开(公告)号:US20060106025A1
公开(公告)日:2006-05-18
申请号:US11231041
申请日:2005-09-20
申请人: Graeme Smith , Niall Martin , Keith Menear , Marc Hummersone , Laurent Rigoreau , Roger Griffin , Bernard Golding , David Newell , Hilary Calvert , Nicola Curtin , Ian Hardcastle , Kappusamy Saravanan
发明人: Graeme Smith , Niall Martin , Keith Menear , Marc Hummersone , Laurent Rigoreau , Roger Griffin , Bernard Golding , David Newell , Hilary Calvert , Nicola Curtin , Ian Hardcastle , Kappusamy Saravanan
IPC分类号: A61K31/496 , C07D409/14
CPC分类号: C07D413/14 , C07D409/04 , C07D409/14
摘要: A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R1 and R2 are independently selected from 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; Q is —NH—C(═O)— or —O—; Y is an optionally substituted C1-5 alkylene group; X is selected from SR3 or NR4R5, wherein, R3, or R4 and R5 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R4 and R5 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; if Q is —O—, X is additionally selected from —C(═O)—NR6R7, wherein R6 and R7 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R6 and R7 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 if Q is —NH—C(═O)—, —Y—X may additionally be selected from C1-7 alkyl.
摘要翻译: 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,其中:R 1和R 2独立地选自氢,任选地 取代的C 1-7烷基,C 3-20杂环基或C 5-20-20芳基,或者可以一起形成 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; Q是-NH-C(-O) - 或-O-; Y是任选取代的C 1-5亚烷基; X选自SR 3或NR 4 R 5,其中R 3,R 3,R 3, 4和R 5独立地选自氢,任选取代的C 1-7 - 烷基,C 5-20-20芳基,或 C 3-20杂环基或R 4和R 5可以一起与它们所连接的氮原子一起形成一个 具有4至8个环原子的任选取代的杂环; 如果Q是-O-,X另外选自-C(-O)-NR 6 R 7,其中R 6和R 独立地选自氢,任选取代的C 1-7 - 烷基,C 5-20-20芳基或C 3-20 或者R 6和R 7可以与它们所连接的氮原子一起形成任选取代的杂环,其具有4个 至8个环原子; 并且如果Q是-NH-C(-O) - ,-Y-X可另外选自C 1-7烷基。
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公开(公告)号:US20120135983A1
公开(公告)日:2012-05-31
申请号:US13286475
申请日:2011-11-01
申请人: Alan Ashworth , Stephen Jackson , Niall Martin , Graeme Smith
发明人: Alan Ashworth , Stephen Jackson , Niall Martin , Graeme Smith
IPC分类号: A61K31/551 , A61P35/00 , G01N33/566 , C12Q1/06 , A61K31/502 , C12Q1/68
CPC分类号: A61K31/366 , A61K31/00 , A61K31/405 , A61K31/4184 , A61K31/4706 , A61K31/473 , A61K31/502 , A61K31/517 , A61K31/522 , A61K31/675 , Y02A50/473
摘要: The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.
摘要翻译: 本发明涉及对在HR依赖性DNA DSB修复缺陷的细胞中碱基切除修复途径的抑制选择性致死的认识。 本文提供了使用靶向基础切除修复组分(如PARP)的抑制剂治疗缺乏HR依赖性DNA DSB修复的癌症治疗方法和手段。
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公开(公告)号:US20060142293A1
公开(公告)日:2006-06-29
申请号:US11352178
申请日:2006-02-10
申请人: Niall Martin , Graeme Smith , Charles White , Roger Newton , Diane Douglas , Penny Eversley , Julia Vile
发明人: Niall Martin , Graeme Smith , Charles White , Roger Newton , Diane Douglas , Penny Eversley , Julia Vile
IPC分类号: A61K31/502
CPC分类号: C07D401/12 , A61K31/50 , A61K31/502 , C07D237/32 , C07D403/12 , C07D405/12 , C07D409/12 , C07D413/12 , C07D417/12
摘要: A method of treatment of a disease of the human or animal body mediated by PARP comprising administering to such a subject a therapeutically effective amount of a compound of formula: or an isomer, salt, solvate, chemically protected form, and prodrug thereof, wherein: A and B together represent an optionally substituted, fused aromatic ring; RC is represented by -L-RL, where L is of formula: —(CH2)n1-Qn2-(CH2)n3— wherein n1, n2 and n3 are each selected from 0, 1, 2 and 3, the sum of n1, n2 and n3 is 1, 2 or 3 and Q is selected from O, S, NH, C(═O) or —CR1R2—, where R1 and R2 are independently selected from hydrogen, halogen or optionally substituted C1-7 alkyl, or may together with the carbon atom to which they are attached form a C3-7 cyclic alkyl group, which may be saturated (a C3-7 cycloalkyl group) or unsaturated (a C3-7 cycloalkenyl group), or one of R1 and R2 may be attached to an atom in RL to form an unsaturated C3-7 cycloalkenyl group which comprises the carbon atoms to which R1 and R2 are attached in Q, —(CH2)n3— (if present) and part of RL; and RL is optionally substituted C5-20 aryl; and RN is selected from hydrogen, optionally substituted C1-7 alkyl, C3-20 heterocyclyl, and C5-20 aryl, hydroxy, ether, nitro, amino, amido, thiol, thioether, sulfoxide and sulfone.
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公开(公告)号:US20060142231A1
公开(公告)日:2006-06-29
申请号:US11245735
申请日:2005-10-06
申请人: Alan Ashworth , Stephen Jackson , Niall Martin , Graeme Smith , Mark O'Connor
发明人: Alan Ashworth , Stephen Jackson , Niall Martin , Graeme Smith , Mark O'Connor
IPC分类号: A61K48/00 , A61K31/522 , A61K31/502 , A61K31/473 , A61K31/517 , A61K31/4704 , A61K31/4035 , A61K31/366
CPC分类号: A61K31/366 , A61K31/405 , A61K31/4184 , A61K31/4706 , A61K31/473 , A61K31/502 , A61K31/517 , A61K31/522 , A61K31/675 , Y02A50/473
摘要: DNA Damage Repair Inhibitors for Treatment of Cancer The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.
摘要翻译: 用于治疗癌症的DNA损伤修复抑制剂本发明涉及对在HR依赖性DNA DSB修复缺陷的细胞中碱基切除修复途径的抑制选择性致死的认识。 本文提供了使用靶向基础切除修复组分(如PARP)的抑制剂治疗缺乏HR依赖性DNA DSB修复的癌症治疗方法和手段。
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公开(公告)号:US08143241B2
公开(公告)日:2012-03-27
申请号:US11245735
申请日:2005-10-06
申请人: Alan Ashworth , Stephen Jackson , Niall Martin , Graeme Smith , Mark O'Connor
发明人: Alan Ashworth , Stephen Jackson , Niall Martin , Graeme Smith , Mark O'Connor
IPC分类号: A61K31/50 , A61K31/44 , A61K31/415 , A01N43/00
CPC分类号: A61K31/366 , A61K31/405 , A61K31/4184 , A61K31/4706 , A61K31/473 , A61K31/502 , A61K31/517 , A61K31/522 , A61K31/675 , Y02A50/473
摘要: The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.
摘要翻译: 本发明涉及对在HR依赖性DNA DSB修复缺陷的细胞中碱基切除修复途径的抑制选择性致死的认识。 本文提供了使用靶向基础切除修复组分(如PARP)的抑制剂治疗缺乏HR依赖性DNA DSB修复的癌症治疗方法和手段。
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