2-chloro-N-methyl-5-(trifluoromethyl)pyridin-4-amine | 1369848-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-chloro-N-methyl-5-(trifluoromethyl)pyridin-4-amine
• 英文别名: 4-Pyridinamine, 2-chloro-N-methyl-5-(trifluoromethyl)-
• CAS: 1369848-46-3
• 化学式: C₇H₆ClF₃N₂
• 分子量: 210.586
• InChiKey: NDYLJCOVZFSKKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-5-amino-3-((1-(dimethylamino)propan-2-yl)oxy)pyrazine-2-carbonitrile 、 2-chloro-N-methyl-5-(trifluoromethyl)pyridin-4-amine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 反应 1.0h， 以66%的产率得到(R)-3-((1-(dimethylamino)propan-2-yl)oxy)-5-((4-(methylamino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile
  参考文献：
  名称：

  Discovery of 3-Alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as Selective, Orally Bioavailable CHK1 Inhibitors

  摘要：

  Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential antitumor agents, but the most advanced inhibitor series reported to date are not orally bioavailable. A novel series of potent and orally bioavailable 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitrile CHK1 inhibitors was generated by hybridization of two lead scaffolds derived from fragment based drug design and optimized for CHK1 potency and high selectivity using a cell based assay cascade. Efficient in vivo pharmacokinetic assessment was used to identify compounds with prolonged exposure following oral dosing. The optimized compound (CCT244747) was a potent and highly selective CHK1 inhibitor, which modulated the DNA damage response pathway in human tumor xenografts and showed antitumor activity in combination with genotoxic chemotherapies and as a single agent

  DOI：

  10.1021/jm3012933
• 作为产物：
  描述：

  甲胺 、 2-氯-5-三氟甲基-4-碘吡啶 以 甲醇 为溶剂， 反应 1.0h， 以31%的产率得到2-chloro-N-methyl-5-(trifluoromethyl)pyridin-4-amine
  参考文献：
  名称：

  [EN] 5-(PYRIDIN-2-YL-AMINO)-PYRAZINE-2-CARBONITRILE COMPOUNDS AND THEIR THERAPEUTIC USE
  [FR] COMPOSÉS DE TYPE 5-(PYRIDIN-2-YL-AMINO)-PYRAZINE-2-CARBONITRILE ET LEUR UTILISATION THÉRAPEUTIQUE

  摘要：

  本发明涉及治疗化合物领域。更具体地，本发明涉及某些吡啶基氨基吡嗪碳腈化合物，该化合物在某种程度上抑制检查点激酶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，以及在体外和体内使用这些化合物和组合物来抑制CHK1激酶功能，并用于治疗由CHK1介导的疾病和症状，这些疾病和症状通过抑制CHK1激酶功能得到缓解，包括增生性疾病如癌症等，可选择与另一药剂组合使用，例如：（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或胸苷酸合成酶（TS）抑制剂；（d）微管靶向剂；和（e）电离辐射。

  公开号：

  WO2013068755A1

文献信息

• PHOSPHOROUS DERIVATIVES AS KINASE INHIBITORS
  申请人：ARIAD PHARMACEUTICALS, INC.

  公开号：US20150225436A1

  公开（公告）日：2015-08-13

  The invention features compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  该发明涉及一般式化合物：其中变量基团如本文所定义，以及它们的制备和使用。
• [EN] 5-(PYRIDIN-2-YL-AMINO)-PYRAZINE-2-CARBONITRILE COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS DE TYPE 5-(PYRIDIN-2-YL-AMINO)-PYRAZINE-2-CARBONITRILE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CANCER REC TECH LTD

  公开号：WO2013068755A1

  公开（公告）日：2013-05-16

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyridyl-amino-pyrazine carbonitrile compounds that, 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 thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

  本发明涉及治疗化合物领域。更具体地，本发明涉及某些吡啶基氨基吡嗪碳腈化合物，该化合物在某种程度上抑制检查点激酶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，以及在体外和体内使用这些化合物和组合物来抑制CHK1激酶功能，并用于治疗由CHK1介导的疾病和症状，这些疾病和症状通过抑制CHK1激酶功能得到缓解，包括增生性疾病如癌症等，可选择与另一药剂组合使用，例如：（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或胸苷酸合成酶（TS）抑制剂；（d）微管靶向剂；和（e）电离辐射。
• PHOSPHORUS DERIVATIVES AS KINASE INHIBITORS
  申请人：Wang Yihan

  公开号：US20120202776A1

  公开（公告）日：2012-08-09

  The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

  该发明涉及通式（I）中变量基团如此定义的化合物，以及它们的制备和使用。
• Phosphorus Derivatives as Kinase Inhibitors
  申请人：ARIAD Pharmaceuticals, Inc.

  公开号：US20130225528A1

  公开（公告）日：2013-08-29

  The invention features compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  该发明涉及一般式化合物：其中变量基团的定义如本文所述，以及它们的制备和使用。
• Phosphorous Derivatives as Kinase Inhibitors
  申请人：ARIAD Pharmaceuticals, Inc.

  公开号：US20160376297A1

  公开（公告）日：2016-12-29

  The invention features compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及一般式化合物：其中变量基团如此定义，以及它们的制备和使用。