5-[[4-[[(2S)-morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile | 1489389-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-[[4-[[(2S)-morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile
• 英文别名: Unii-lcr5pkk3H6；5-[[4-[[(2S)-morpholin-2-yl]methylamino]-5-(trifluoromethyl)pyridin-2-yl]amino]pyrazine-2-carbonitrile
• CAS: 1489389-23-2
• 化学式: C₁₆H₁₆F₃N₇O
• 分子量: 379.345
• InChiKey: YBYYWUUUGCNAHQ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-(S)-2-吗啉甲醇 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三异丙基硅烷 、 sodium hydride 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 43.17h， 生成 5-[[4-[[(2S)-morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile
  参考文献：
  名称：

  [EN] 5-[[4-[[MORPHOLIN-2-YL]METHYLAMINO]-5-(TRIFLUOROMETHYL)-2-PYRIDYL]AMINO]PYRAZINE-2-CARBONITRILE AND THERAPEUTIC USES THEREOF
  [FR] 5-[[4-[[MORPHOLIN-2-YL]MÉTHYLAMINO]-5-(TRIFLUOROMÉTHYL)-2-PYRIDYL]- AMINO]PYRAZINE-2-CARBONITRILE ET UTILISATIONS THÉRAPEUTIQUES DE CELUI-CI

  摘要：

  本发明涉及治疗化合物领域。更具体地，本发明涉及5-[[4-[[吗啡啶-2-基]甲基氨基]-5-(三氟甲基)-2-吡啶基]氨基]吡嗪-2-碳腈化合物（以下简称为“TFM化合物”），其中包括抑制检查点激酶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，以及使用这些化合物和组合物，无论是体外还是体内，来抑制CHK1激酶功能，并用于治疗由CHK1介导的疾病和症状，通过抑制CHK1激酶功能得以改善，等等，包括增殖性疾病如癌症等，可选地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）微管靶向药物；（e）电离辐射；（f）一个有丝分裂调节因子或有丝分裂检查点调节因子的抑制剂；（g）DNA损伤信号传导物的抑制剂；或（h）DNA损伤修复酶的抑制剂。

  公开号：

  WO2013171470A1

文献信息

• 5-[[4-[[MORPHOLIN-2-YL]METHYLAMINO]-5-(TRIFLUOROMETHYL)-2-PYRIDYL]AMINO]PYRAZINE-2-CARBONITRILE AND THERAPEUTIC USES THEREOF
  申请人：Cancer Research Technology Limited

  公开号：US20150126471A1

  公开（公告）日：2015-05-07

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as “TFM 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 a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.

  本发明涉及治疗化合物领域。更具体地，本发明涉及5-[[4-[[吗啡啉-2-基]甲基氨基]-5-(三氟甲基)-2-吡啶基]氨基]吡嗪-2-羧腈化合物（以下简称“TFM化合物”），其抑制检查点激酶1（CHK1）激酶功能等。本发明还涉及包含此类化合物的制药组合物，以及在体内外使用此类化合物和组合物来抑制CHK1激酶功能，以及治疗由CHK1介导的疾病和情况，通过抑制CHK1激酶功能来缓解的疾病和情况等，包括增生性疾病，如癌症等，可选地与另一种药物联合使用，例如：（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或胸腺嘧啶酸合成酶（TS）抑制剂；（d）微管靶向药物；（e）电离辐射；（f）减数分裂调节因子或有丝分裂检查点调节因子的抑制剂；（g）DNA损伤信号传导体的抑制剂；或（h）DNA损伤修复酶的抑制剂。
• PROCESS FOR MANUFACTURING 5-[[4-[[MORPHOLIN-2-YL]METHYLAMINO]-5-(TRIFLUOROMETHYL)- 2-PYRIDYL]AMINO]PYRAZINE-2-CARBONITRILE
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：EP3210980A1

  公开（公告）日：2017-08-30

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as "TFM 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 a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.

  本发明一般涉及治疗化合物领域。 更具体地说，本发明涉及5-[[4-[[吗啉-2-基]甲基氨基]-5-(三氟甲基)-2-吡啶基]氨基]吡嗪-2-甲腈化合物（本文称为 "TFM化合物"），该化合物除其他外能抑制检查点激酶1（CHK1）激酶的功能。本发明还涉及包含此类化合物的药物组合物，以及此类化合物和组合物在体外和体内抑制 CHK1 激酶功能的用途，以及在治疗由 CHK1 介导的、通过抑制 CHK1 激酶功能而得到改善的疾病和病症等方面的用途，包括癌症等增殖性病症、可选择与另一种制剂联合使用，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) 微管靶向制剂；(e) 电离辐射；(f) 有丝分裂调节剂或有丝分裂检查点调节剂的抑制剂；(g) DNA 损伤信号转导物的抑制剂；或 (h) DNA 损伤修复酶的抑制剂。
• 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2 pyridyl]amino]pyrazine-2-carbonitrile and therapeutic uses thereof
  申请人：Cancer Research Technology Limited

  公开号：US10259806B2

  公开（公告）日：2019-04-16

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as “TFM 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 a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionizing radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.

  本发明一般涉及治疗化合物领域。更具体地说，本发明涉及5-[[4-[[吗啉-2-基]甲基氨基]-5-(三氟甲基)-2-吡啶基]氨基]吡嗪-2-甲腈化合物（本文称为 "TFM化合物"），该化合物除其他外能抑制检查点激酶1（CHK1）激酶的功能。本发明还涉及包含此类化合物的药物组合物，以及此类化合物和组合物在体外和体内抑制 CHK1 激酶功能的用途，以及在治疗由 CHK1 介导的、通过抑制 CHK1 激酶功能而得到改善的疾病和病症等方面的用途，包括癌症等增殖性病症、可选择与另一种制剂联合使用，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) 微管靶向制剂；(e) 电离辐射；(f) 有丝分裂调节剂或有丝分裂检查点调节剂的抑制剂；(g) DNA 损伤信号转导物的抑制剂；或 (h) DNA 损伤修复酶的抑制剂。
• 5-[[4-[[Morpholin-2-yl]Methylamino]-5-(Trifluoromethyl)-2 Pyridyl]Amino]Pyrazine-2-Carbonitrile and Therapeutic Uses Thereof
  申请人：Cancer Research Technology Limited

  公开号：US20180022739A1

  公开（公告）日：2018-01-25

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as “TFM 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 a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.
• US9663503B2
  申请人：——

  公开号：US9663503B2

  公开（公告）日：2017-05-30