ethyl 4-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-2-(methylthio)pyrimidine-5-carboxylate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-2-(methylthio)pyrimidine-5-carboxylate
• 英文别名: ethyl 4-[4-(2-carbamoylpyridin-4-yl)oxy-3-fluoroanilino]-2-methylsulfanylpyrimidine-5-carboxylate
• 化学式: C₂₀H₁₈FN₅O₄S
• 分子量: 443.458
• InChiKey: ATDNUELJLPUFLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-2-(methylthio)pyrimidine-5-carboxylate 在 镍 作用下， 以 乙醇 、 水 为溶剂， 反应 16.0h， 以to give the desired product (91 mg, 39%) as a solid的产率得到ethyl 4-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)pyrimidine-5-carboxylate
  参考文献：
  名称：

  MET kinase inhibitors

  摘要：

  本发明涉及具有I或II公式的化合物，包括其盐，并且涉及使用它们用于癌症的治疗方法。

  公开号：

  US20070078140A1
• 作为产物：
  描述：

  4-(4-氨基-2-氟苯氧基)吡啶酰胺 、 4-氯-2-甲硫基嘧啶-5-羧酸乙酯 在 盐酸 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 水 为溶剂， 以93%的产率得到ethyl 4-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-2-(methylthio)pyrimidine-5-carboxylate
  参考文献：
  名称：

  Design, synthesis and structure–activity relationships of novel biarylamine-based Met kinase inhibitors

  摘要：

  Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.042

文献信息

• MET kinase inhibitors
  申请人：Borzilleri M. Robert

  公开号：US20070078140A1

  公开（公告）日：2007-04-05

  The present invention is directed to compounds having the formula I or II: including salts thereof, and methods for using them for the treatment of cancer.

  本发明涉及具有以下化学式I或II的化合物：包括其盐，并且使用它们用于治疗癌症的方法。
• MET KINASE INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1937682A1

  公开（公告）日：2008-07-02
• US7547782B2
  申请人：——

  公开号：US7547782B2

  公开（公告）日：2009-06-16
• [EN] MET KINASE INHIBITORS<br/>[FR] INHIBITEURS DE MET KINASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2007041379A1

  公开（公告）日：2007-04-12

  [EN] The present invention is directed to compounds having the formula I or II including salts thereof, and methods for using them for the treatment of cancer.
  [FR] La présente invention concerne des composés de formule (I) ou (II) et leurs sels, ainsi que des méthodes d'utilisation desdits composés pour le traitement du cancer.
• Design, synthesis and structure–activity relationships of novel biarylamine-based Met kinase inhibitors
  作者：David K. Williams、Xiao-Tao Chen、Christine Tarby、Robert Kaltenbach、Zhen-Wei Cai、John S. Tokarski、Yongmi An、John S. Sack、Barri Wautlet、Johnni Gullo-Brown、Benjamin J. Henley、Robert Jeyaseelan、Kristen Kellar、Veeraswamy Manne、George L. Trainor、Louis J. Lombardo、Joseph Fargnoli、Robert M. Borzilleri

  DOI：10.1016/j.bmcl.2010.01.042

  日期：2010.5

  Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.