N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine | 1431872-18-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine
• 英文别名: N-(2-Fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine；N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methylpyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine
• CAS: 1431872-18-2
• 化学式: C₂₃H₂₁FN₈O₂
• 分子量: 460.471
• InChiKey: PEVJRHJJWVYDQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine 在 盐酸 作用下， 以 乙醇 、 乙腈 为溶剂， 以78%的产率得到C₂₃H₂₁FN₈O₂*1.76ClH
  参考文献：
  名称：

  [EN] ANTICANCER PYRIDOPYRAZINES VIA THE INHIBITION OF FGFR KINASES
  [FR] PYRIDOPYRAZINES ANTI-CANCÉREUSES PAR L'INHIBITION DE KINASES DE FGFR

  摘要：

  这项发明涉及新的吡啶吡嗪衍生物化合物，包括含有该化合物的药物组合物，制备该化合物的方法以及利用该化合物治疗疾病，例如癌症。

  公开号：

  WO2013061080A1
• 作为产物：
  描述：

  C₂₅H₂₆FN₉O₄S 在 盐酸 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以60%的产率得到N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine
  参考文献：
  名称：

  [EN] ANTICANCER PYRIDOPYRAZINES VIA THE INHIBITION OF FGFR KINASES
  [FR] PYRIDOPYRAZINES ANTI-CANCÉREUSES PAR L'INHIBITION DE KINASES DE FGFR

  摘要：

  这项发明涉及新的吡啶吡嗪衍生物化合物，包括含有该化合物的药物组合物，制备该化合物的方法以及利用该化合物治疗疾病，例如癌症。

  公开号：

  WO2013061080A1

文献信息

• [EN] A DEUTERATED TRIAZOLOPYRIDAZINE AS A KINASE MODULATOR<br/>[FR] TRIAZOLOPYRIDAZINE DEUTÉRÉE EN TANT QUE MODULATEUR DE KINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2016087586A1

  公开（公告）日：2016-06-09

  The invention is directed to a triazolopyridazine compound of formula (I), N-oxides, pharmaceutically acceptable salts and solvates thereof, wherein D represents deuterium, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

  该发明涉及一种三唑吡嗪化合物，其化学式为（I），以及其氮氧化物、药学上可接受的盐和溶剂化物，其中D代表氘。该化合物的用途为蛋白酪氨酸激酶调节剂，特别是c-Met的抑制剂，并用于减少或抑制细胞或主体中c-Met的激酶活性，并调节细胞或主体中c-Met的表达。该化合物的用途还包括预防或治疗细胞增殖紊乱和/或与c-Met相关的疾病。本发明还涉及包含该化合物的制药组合物以及治疗癌症和其他细胞增殖紊乱的方法。
• COMBINATIONS OF AN FGFR INHIBITOR AND AN IGF1R INHIBITOR
  申请人：Astex Therapeutics Ltd

  公开号：US20170100406A1

  公开（公告）日：2017-04-13

  The invention relates to a combination of a FGFR inhibitor and an IGF1R inhibitor. The combination is for use in the treatment of a proliferative disorder, in particular for the treatment of cancer. The FGFR inhibitor and the IGFR inhibitor can be administered simultaneously, separately or sequentially. The invention further relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a combination according to the invention.

  本发明涉及一种FGFR抑制剂和IGF1R抑制剂的组合。该组合用于治疗增生性疾病，特别是用于治疗癌症。FGFR抑制剂和IGFR抑制剂可以同时、分开或顺序给药。本发明还涉及一种制药组合物，包括一种药学上可接受的载体和本发明的组合物。
• CMET-INHIBITORS FOR USE IN DELAYING THE EMERGENCE IN RESISTANCE TO FGFR INHIBITORS
  申请人：Astex Therapeutics Limited

  公开号：EP3848034A1

  公开（公告）日：2021-07-14

  The invention relates to a combination of a first compound selected from N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof; and a second compound which is a cMet inhibitor. The combination is for use in the treatment of a proliferative disorder, in particular for use in the treatment of cancer. The FGFR inhibitor (N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof) and the cMet inhibitor can be administered simultaneously, separately or sequentially. The invention further relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a combination according to the invention.

  本发明涉及选自 N-(3,5-二甲氧基苯基)-N'-(1-甲基乙基)-N-[3-(1-甲基-1H-吡唑-4-基)喹喔啉-6-基]乙烷-1,2-二胺或其药学上可接受的盐或其溶液的第一种化合物的组合、和 N-(2-氟-3,5-二甲氧基苯基)-N-(1H-咪唑-2-基甲基)-3-(1-甲基-1H-吡唑-4-基)吡啶并[2,3-b]吡嗪-6-胺或其药学上可接受的盐或其溶液；第二种化合物是一种 cMet 抑制剂。 该组合物用于治疗增殖性疾病，特别是用于治疗癌症。 FGFR抑制剂（N-(3,5-二甲氧基苯基)-N'-(1-甲基乙基)-N-[3-(1-甲基-1H-吡唑-4-基)喹喔啉-6-基]乙烷-1,2-二胺或其药学上可接受的盐或其溶液，以及N-(2-氟-3、5-二甲氧基苯基)-N-(1H-咪唑-2-基甲基)-3-(1-甲基-1H-吡唑-4-基)吡啶并[2,3-b]吡嗪-6-胺或其药学上可接受的盐或其溶液)和 cMet 抑制剂可同时、分别或依次给药。 本发明还涉及一种药物组合物，该组合物包含药学上可接受的载体和根据本发明的组合物。
• Combinations
  申请人：ASTEX THERAPEUTICS LTD

  公开号：US10085982B2

  公开（公告）日：2018-10-02

  The invention relates to a combination of a first compound selected from N-(3,5-dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof; and a second compound which is a cMet inhibitor. The combination is for use in the treatment of a proliferative disorder, in particular for use in the treatment of cancer. The FGFR inhibitor (N-(3,5-dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof) and the cMet inhibitor can be administered simultaneously, separately or sequentially. The invention further relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a combination according to the invention.

  本发明涉及选自 N-(3,5-二甲氧基苯基)-N′-(1-甲基乙基)-N-[3-(1-甲基-1H-吡唑-4-基)喹喔啉-6-基]乙烷-1,2-二胺或其药学上可接受的盐或其溶液的第一种化合物的组合、和 N-(2-氟-3,5-二甲氧基苯基)-N-(1H-咪唑-2-基甲基)-3-(1-甲基-1H-吡唑-4-基)吡啶并[2,3-b]吡嗪-6-胺或其药学上可接受的盐或其溶液；第二种化合物是一种 cMet 抑制剂。该组合物用于治疗增殖性疾病，特别是用于治疗癌症。FGFR抑制剂（N-(3,5-二甲氧基苯基)-N′-(1-甲基乙基)-N-[3-(1-甲基-1H-吡唑-4-基)喹喔啉-6-基]乙烷-1,2-二胺或其药学上可接受的盐或其溶液，以及N-(2-氟-3、5-二甲氧基苯基)-N-(1H-咪唑-2-基甲基)-3-(1-甲基-1H-吡唑-4-基)吡啶并[2,3-b]吡嗪-6-胺或其药学上可接受的盐或其溶液)和 cMet 抑制剂可同时、分别或依次给药。本发明还涉及一种药物组合物，该组合物包含药学上可接受的载体和根据本发明的组合物。
• Deuterated triazolopyridazine as a kinase modulator
  申请人：Janssen Pharmaceutica NV

  公开号：US10138246B2

  公开（公告）日：2018-11-27

  The invention is directed to a triazolopyridazine compound of formula (I), N-oxides, pharmaceutically acceptable salts and solvates thereof, wherein D represents deuterium, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

  本发明涉及式(I)的三唑并哒嗪化合物、其N-氧化物、药学上可接受的盐和溶剂（其中D代表氘），以及将此类化合物用作蛋白酪氨酸激酶调节剂，特别是c-Met的抑制剂、以及使用此类化合物降低或抑制细胞或受试者中c-Met的激酶活性，调节细胞或受试者中c-Met的表达，以及使用此类化合物预防或治疗受试者中细胞增殖障碍和/或与c-Met相关的疾病。本发明进一步涉及包含本发明化合物的药物组合物，以及治疗癌症和其他细胞增殖障碍等疾病的方法。