公开(公告)号：US20110224274A1

公开(公告)日：2011-09-15

申请号：US13001372

申请日：2009-06-25

申请人： Bernard Thomas Golding ,  Christiane Riedinger ,  Roger John Griffin ,  Ian Robert Hardcasctle ,  Eric Valeur ,  Anna Frances Watson ,  Martin Noble

发明人： Bernard Thomas Golding ,  Christiane Riedinger ,  Roger John Griffin ,  Ian Robert Hardcasctle ,  Eric Valeur ,  Anna Frances Watson ,  Martin Noble

IPC分类号： A61K31/4035 ,  C07D209/48 ,  A61P35/00 ,  A61K31/403

CPC分类号： C07D209/49 ,  A61K31/4035 ,  A61K31/4402 ,  A61K45/06 ,  C07D209/48 ,  C07D401/06 ,  C07D403/06

摘要： A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.

摘要翻译： 式（I）化合物或式（II）化合物或其药学上可接受的盐，其中R 1 -R 7和X如说明书中所定义，以及这些化合物在治疗中的用途，特别是在治疗癌症或作为 MDM2蛋白与p53相互作用的抑制剂。

公开(公告)号：US07642254B2

公开(公告)日：2010-01-05

申请号：US11351052

申请日：2006-02-09

申请人： Marc Geoffrey Hummersone ,  Keith Allan Menear ,  Laurent Jean Martin Rigoreau ,  Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Roger John Griffin

发明人： Marc Geoffrey Hummersone ,  Keith Allan Menear ,  Laurent Jean Martin Rigoreau ,  Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Roger John Griffin

IPC分类号： A61K31/535 ,  A61K31/38 ,  A61K31/35 ,  C07D413/14 ,  C07D409/14 ,  C07D407/14

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，溶剂合物，化学保护形式及其前药，其中：R 1和R 2一起与它们所连接的氮原子一起形成任选取代的含氮杂环，其具有4个 至8个环原子; 并且R 3选自羟基和-NRN 1 R N 2，其中RN 1和RN 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芳基，或一起形成， 与它们相连的氮原子，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。

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，

公开(公告)号：US07696203B2

公开(公告)日：2010-04-13

申请号：US11403606

申请日：2006-04-13

申请人： Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Keith Allan Menear ,  Marc Geoffrey Hummersone ,  Xiao-ling Cockcroft ,  Mark Frigerio ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Kappusamy Saravanan ,  Marine Desage-El Murr

发明人： Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Keith Allan Menear ,  Marc Geoffrey Hummersone ,  Xiao-ling Cockcroft ,  Mark Frigerio ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  David Richard Newell ,  Hilary Alan Calvert ,  Nicola Jane Curtin ,  Kappusamy Saravanan ,  Marine Desage-El Murr

IPC分类号： A61K31/535 ,  C07D413/14

CPC分类号： C07D413/00 ,  C07D401/14 ,  C07D405/04 ,  C07D407/04 ,  C07D407/14 ,  C07D409/04 ,  C07D471/04

摘要： Compounds of formula I: wherein A, B and D are respectively selected from the group consisting of: (i) CH, NH, C; (ii) CH, N, N; and (iii) CH, O, C; the dotted lines represent two double bonds in the appropriate locations; and where Z is selected from S, O, C(═O), CH2 and NH are disclosed for use in inhibiting DNA-PK.

摘要翻译： 式I化合物：其中A，B和D分别选自：（i）CH，NH，C; （ii）CH，N，N; 和（iii）CH，O，C; 虚线表示适当位置的两个双键; 并且其中Z选自S，O，C（= O），CH 2和NH用于抑制DNA-PK。

公开(公告)号：US20090043091A1

公开(公告)日：2009-02-12

申请号：US12233736

申请日：2008-09-19

申请人： Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Laurent Jean Martin Rigoreau ,  Marc Geoffrey Hummersone ,  Roger John Griffin

发明人： Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Laurent Jean Martin Rigoreau ,  Marc Geoffrey Hummersone ,  Roger John Griffin

IPC分类号： C07D243/08 ,  C07D413/14 ,  C07D223/02 ,  C07D279/18

CPC分类号： C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

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 heterocyclic ring having from 4 to 8 ring atoms; and RN1 is selected from hydrogen, an optionally substituted C1-7 alkyl group, an optionally substituted C3-20 heterocyclyl group, an optionally substituted C5-20 aryl group, an acyl group, an ester group and an amido group, and its use as a pharmaceutical.

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 2一起与它们所连接的氮原子一起形成任选取代的具有4至8个的杂环 环原子 并且RN1选自氢，任选取代的C 1-7烷基，任选取代的C 3-20杂环基，任选取代的C 5-20芳基，酰基，酯基和酰胺基，其用作 制药。

公开(公告)号：US08258175B2

公开(公告)日：2012-09-04

申请号：US11574531

申请日：2005-08-26

申请人： Hendrika Maria Gerarda Willems ,  Per Kallblad ,  Ian Robert Hardcastle ,  Roger John Griffin ,  Bernard Thomas Golding ,  John Lunec ,  Martin E. M. Noble ,  David R. Newell ,  Alan H. Calvert

发明人： Hendrika Maria Gerarda Willems ,  Per Kallblad ,  Ian Robert Hardcastle ,  Roger John Griffin ,  Bernard Thomas Golding ,  John Lunec ,  Martin E. M. Noble ,  David R. Newell ,  Alan H. Calvert

IPC分类号： A61K31/4015 ,  C07D209/46

CPC分类号： C07D209/50 ,  C07D209/48 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12

摘要： A compound of formula or a prodrug and/or a pharmaceutically acceptable salt thereof, wherein X is O, N or S; R1 is hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroaralkyl; R2 is hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; R3 is hydrogen, halo, hydroxy, substituted or unsubstituted alloy substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; and R4-R7, is used to represent groups R4, R5, R6 and R7 which are H, OH, alkyl, alkoxy, alkylamine, hydroxyalkyl, halo, CF3, NH2, NO2, COOH, C═O.

摘要翻译： 式或其前药和/或其药学上可接受的盐的化合物，其中X为O，N或S; 取代或未取代的烷基胺，烷氧基，取代或未取代的芳基或杂芳基，以及取代或未取代的芳烷基或杂芳烷基; R 1为氢，卤素，羟基， R2是氢，卤素，羟基，取代或未取代的烷基，取代或未取代的羟基烷基取代或未取代的烷基胺，烷氧基，取代或未取代的芳基或杂芳基，以及取代或未取代的芳烷基或杂烷基; 取代或未取代的烷基胺烷氧基，取代或未取代的芳基或杂芳基，以及取代或未取代的芳烷基或杂烷基; R 3为氢，卤素，羟基， H，OH，烷基，烷氧基，烷基胺，羟基烷基，卤素，CF 3，NH 2，NO 2，COOH，C = O的基团R 4，R 5，R 6和R 7。

公开(公告)号：US20110130386A1

公开(公告)日：2011-06-02

申请号：US12989510

申请日：2009-04-24

申请人： Mark Frigerio ,  Heather Mary Ellen Duggan ,  Marc Geoffrey Hummersone ,  Keith Allan Menear ,  Niall Morrison Barr Martin ,  Celine Cano ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle

发明人： Mark Frigerio ,  Heather Mary Ellen Duggan ,  Marc Geoffrey Hummersone ,  Keith Allan Menear ,  Niall Morrison Barr Martin ,  Celine Cano ,  Roger John Griffin ,  Bernard Thomas Golding ,  Ian Robert Hardcastle

IPC分类号： A61K31/551 ,  C07D413/14 ,  C07D243/06 ,  C12N5/071 ,  A61K31/5355 ,  A61K31/55 ,  A61P35/00

CPC分类号： C07D413/14 ,  C07D417/14

摘要： A compound of formula (I) 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; and RN1 and RN2 are 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.

摘要翻译： 式（I）的化合物，其中：R 1和R 2独立地选自氢，任选取代的C 1-7烷基，C 3-20杂环基或C 5-20芳基，或者可以与氮原子一起形成 与它们相连的任选取代的具有4至8个环原子的杂环; 并且RN1和RN2选自氢，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至8个环原子的杂环。

公开(公告)号：US6015827A

公开(公告)日：2000-01-18

申请号：US56928

申请日：1998-04-08

申请人： Roger John Griffin ,  Alan Hilary Calvert ,  Nicola Jane Curtin ,  David Richard Newell ,  Bernard Thomas Golding

发明人： Roger John Griffin ,  Alan Hilary Calvert ,  Nicola Jane Curtin ,  David Richard Newell ,  Bernard Thomas Golding

IPC分类号： C07D239/90 ,  A61K31/135 ,  A61K31/275 ,  A61K31/357 ,  A61K31/36 ,  A61K31/39 ,  A61K31/42 ,  A61K31/423 ,  A61K31/496 ,  A61K31/505 ,  A61K31/517 ,  A61K45/00 ,  A61N5/00 ,  A61P35/00 ,  A61P43/00 ,  C07C235/46 ,  C07C247/16 ,  C07C255/54 ,  C07D239/91 ,  C07D263/56 ,  C07D263/57 ,  C07D317/54 ,  C07D317/68 ,  C07D327/04 ,  C07D473/34 ,  C07D473/40 ,  C07D413/02

CPC分类号： C07D263/56 ,  C07C235/46 ,  C07C247/16 ,  C07C255/54 ,  C07D239/91 ,  C07D263/57 ,  C07D317/68 ,  C07D473/34 ,  C07D473/40

摘要： Benzoxazole carboxamides are disclosed which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. Representative of the compounds are 2-methyl, 2-t-butyl, 2-phenyl or 2-(4-methoxyphenyl) benzoxazole-4-carboxamide.

摘要翻译： 公开了苯并恶唑甲酰胺，其可以作为DNA修复酶聚（ADP-核糖）聚合酶或PARP酶（EC 2.4.2.30）的有效抑制剂，由此可以提供与DNA损伤性细胞毒性药物结合使用的有用的治疗化合物 或放射治疗以增强后者的作用。 化合物的代表是2-甲基，2-叔丁基，2-苯基或2-（4-甲氧基苯基）苯并恶唑-4-甲酰胺。

公开(公告)号：US08618158B2

公开(公告)日：2013-12-31

申请号：US13001372

申请日：2009-06-25

申请人： Bernard Thomas Golding ,  Christiane Riedinger ,  Roger John Griffin ,  Ian Robert Hardcastle ,  Eric Valeur ,  Anna Frances Watson ,  Martin Noble

发明人： Bernard Thomas Golding ,  Christiane Riedinger ,  Roger John Griffin ,  Ian Robert Hardcastle ,  Eric Valeur ,  Anna Frances Watson ,  Martin Noble

IPC分类号： A61K31/4035 ,  C07D207/46

CPC分类号： C07D209/49 ,  A61K31/4035 ,  A61K31/4402 ,  A61K45/06 ,  C07D209/48 ,  C07D401/06 ,  C07D403/06

摘要： A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.

摘要翻译： 式（I）化合物或式（II）化合物或其药学上可接受的盐，其中R 1 -R 7和X如说明书中所定义，以及这些化合物在治疗中的用途，特别是在治疗癌症或作为 MDM2蛋白与p53相互作用的抑制剂。

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。