公开(公告)号：US08367658B2

公开(公告)日：2013-02-05

申请号：US13241887

申请日：2011-09-23

申请人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

发明人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

IPC分类号： A61K31/55 ,  A61K31/5377 ,  A61K31/497 ,  A61K31/506

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin-2-yl-pyridin-2-yl-amine and pyrazine-2-yl-pyrimidin-4-yl-amine compounds, which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及某些联芳基胺化合物（本文称为BAA化合物），特别是某些吡嗪-2-基 - 吡啶-2-基 - 胺和吡嗪-2-基 - 嘧啶-4-基 - 胺化合物，其特别地抑制检测点激酶1（CHK1）激酶功能。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制CHK1激酶功能，以及治疗由CHK1介导的疾病和病症，即 通过抑制CHK1激酶功能等改善，包括增殖条件如癌症等，任选地与另一种试剂组合，例如（a）DNA拓扑异构酶I或II抑制剂; （b）DNA损伤剂; （c）抗代谢物或TS抑制剂; （d）微管靶向剂; 和（e）电离辐射。

公开(公告)号：US20100311730A1

公开(公告)日：2010-12-09

申请号：US12680891

申请日：2008-10-06

申请人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

发明人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

IPC分类号： A61K31/55 ,  C07D401/14 ,  A61K31/506 ,  A61P35/00 ,  C12N9/99 ,  C12N5/02 ,  C07D413/14 ,  A61K31/5377 ,  A61K31/497

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin-2-yl-pyridin-2-yl-amine and pyrazine-2-yl-pyrimidin-4-yl-amine compounds of formula (I), which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionisiπq radiation. wherein: —X═ is independently —CRA5═ or —N═; and the rest of the substituents are as specified in the claims.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及某些联芳基胺化合物（本文称为BAA化合物），特别是某些吡嗪-2-基 - 吡啶-2-基 - 胺和吡嗪-2-基 （I）的嘧啶-4-基 - 胺化合物，其特别地抑制检测点激酶1（CHK1）激酶功能。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制CHK1激酶功能，以及治疗由CHK1介导的疾病和病症，即 通过抑制CHK1激酶功能等改善，包括增殖条件如癌症等，任选地与另一种试剂组合，例如（a）DNA拓扑异构酶I或II抑制剂; （b）DNA损伤剂; （c）抗代谢物或TS抑制剂; （d）微管靶向剂; 和（e）电离辐射。 其中：-X =独立地为-CRA5 =或-N =; 并且其余的取代基如权利要求中所述。

公开(公告)号：US08058045B2

公开(公告)日：2011-11-15

申请号：US12680891

申请日：2008-10-06

申请人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

发明人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

IPC分类号： A61P35/00 ,  A61K31/55 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/497 ,  C07D401/14 ,  C07D413/14 ,  C12N9/99 ,  C12N5/02

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin-2-yl-pyridin-2-yl-amine and pyrazine-2-yl-pyrimidin-4-yl-amine compounds of formula (I), which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionisiπq radiation, wherein: —X═ is independently —CRA5═ or —N═; and the rest of the substituents are as specified in the claims.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及某些联芳基胺化合物（本文称为BAA化合物），特别是某些吡嗪-2-基 - 吡啶-2-基 - 胺和吡嗪-2-基 （I）的嘧啶-4-基 - 胺化合物，其特别地抑制检测点激酶1（CHK1）激酶功能。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制CHK1激酶功能，以及治疗由CHK1介导的疾病和病症，即 通过抑制CHK1激酶功能等改善，包括增殖条件如癌症等，任选地与另一种试剂组合，例如（a）DNA拓扑异构酶I或II抑制剂; （b）DNA损伤剂; （c）抗代谢物或TS抑制剂; （d）微管靶向剂; 和（e）电离辐射，其中：-X =独立地是-CRA5 =或-N =; 并且其余的取代基如权利要求中所述。

公开(公告)号：US20120040967A1

公开(公告)日：2012-02-16

申请号：US13241887

申请日：2011-09-23

申请人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

发明人： Ian Collins ,  John Charles Reader ,  Thomas Peter Matthews ,  Kwai Ming Cheung ,  Nicolas Proisy ,  David Hugh Williams ,  Sukhbinder Singh Klair ,  Jane Elizabeth Scanlon ,  Nelly Piton ,  Glynn Jonathan Addison ,  Michael Cherry

IPC分类号： A61K31/506 ,  C07D413/14 ,  C12N9/99 ,  A61K31/55 ,  A61K31/497 ,  A61P35/00 ,  C07D401/14 ,  A61K31/5377

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin-2-yl-pyridin-2-yl-amine and pyrazine-2-yl-pyrimidin-4-yl-amine compounds, which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及某些联芳基胺化合物（本文称为BAA化合物），特别是某些吡嗪-2-基 - 吡啶-2-基 - 胺和吡嗪-2-基 - 嘧啶-4-基 - 胺化合物，其特别地抑制检测点激酶1（CHK1）激酶功能。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制CHK1激酶功能，以及治疗由CHK1介导的疾病和病症，即 通过抑制CHK1激酶功能等改善，包括增殖条件如癌症等，任选地与另一种试剂组合，例如（a）DNA拓扑异构酶I或II抑制剂; （b）DNA损伤剂; （c）抗代谢物或TS抑制剂; （d）微管靶向剂; 和（e）电离辐射。