(E)-2-(1-(3-((7-fluoroquinolin-6-yl)methyl)imidazo[1,2-b]pyridazin-6-yl)ethylidene)hydrazinecarboxamide | 1266236-84-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (E)-2-(1-(3-((7-fluoroquinolin-6-yl)methyl)imidazo[1,2-b]pyridazin-6-yl)ethylidene)hydrazinecarboxamide
• 英文别名: [(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]urea
• CAS: 1266236-84-3
• 化学式: C₁₉H₁₆FN₇O
• 分子量: 377.381
• InChiKey: MKXUOJJCQVPIMD-BHGWPJFGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-溴-7-氟喹啉 在 四(三苯基膦)钯 盐酸 、 乙基溴化镁 、 水 、 碘 、 sodium formate 、 次磷酸 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~120.0 ℃ 、1.0 MPa 条件下， 反应 9.5h， 生成 (E)-2-(1-(3-((7-fluoroquinolin-6-yl)methyl)imidazo[1,2-b]pyridazin-6-yl)ethylidene)hydrazinecarboxamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC HYDRAZONE COMPOUNDS AND THEIR USES TO TREAT CANCER AND INFLAMMATION
  [FR] COMPOSÉS HYDRAZONE HÉTÉROCYCLIQUES ET LEURS UTILISATIONS POUR TRAITER LE CANCER ET L'INFLAMMATION

  摘要：

  该发明涉及公式(I)的化合物及其盐：其中取代基如规范中所定义；公式(I)的化合物用于治疗人体或动物体，特别是针对c-Met酪氨酸激酶介导的疾病或症状；公式(I)的化合物用于制造治疗此类疾病的药物；包含公式(I)的化合物的药物组合物，可选地与组合伙伴一起，并且公式(I)的化合物的制备方法。

  公开号：

  WO2011018454A1

文献信息

• Combination Products with Tyrosine Kinase Inhibitors and their Use
  申请人：Novartis AG

  公开号：US20180098995A1

  公开（公告）日：2018-04-12

  The present invention relates to pharmaceutical products comprising a combination of (i) a MET inhibitor and (ii) an EGFR inhibitor, or a pharmaceutically acceptable salt thereof, respectively, or a prodrug thereof, which are jointly active in the treatment of proliferative diseases, corresponding pharmaceutical formulations, uses, methods, processes, commercial packages and related invention embodiments.

  本发明涉及一种药物产品，该药物产品包含组合物(i) MET抑制剂和(ii) EGFR抑制剂，或其药学上可接受的盐，或其前药，它们在治疗增生性疾病中具有联合作用，相应的药物制剂、用途、方法、过程、商业包装和相关发明实施例。
• HETEROCYCLIC HYDRAZONE COMPOUNDS
  申请人：He Feng

  公开号：US20120142681A1

  公开（公告）日：2012-06-07

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  本发明涉及式（I）的化合物及其盐：其中取代基如说明书所定义；式（I）的化合物用于治疗人体或动物体，特别是涉及c-Met酪氨酸激酶介导的疾病或病症；使用式（I）的化合物制造用于治疗此类疾病的药物；包含式（I）的化合物的药物组合物，可选地与组合伙伴共存，以及制备式（I）的化合物的过程。
• Heterocyclic hydrazone compounds
  申请人：He Feng

  公开号：US08497368B2

  公开（公告）日：2013-07-30

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  本发明涉及化合物的公式（I）及其盐：其中取代基的定义如规范中所述；化合物的公式（I）用于治疗人体或动物体，特别是与c-Met酪氨酸激酶介导的疾病或状况有关；化合物的公式（I）的用途用于制造用于治疗此类疾病的药物；包含化合物的公式（I）的制药组合物，可选择在合作伙伴的存在下，以及制备化合物的公式（I）的过程。
• 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。