6-(1-methyl-1H-pyrazol-4-yl)-2-(3-((4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)benzyl)pyridazin-3(2H)-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(1-methyl-1H-pyrazol-4-yl)-2-(3-((4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)benzyl)pyridazin-3(2H)-one
• 英文别名: 6-(1-Methylpyrazol-4-yl)-2-[[3-[[4-(1-methylpyrazol-4-yl)pyrimidin-2-yl]amino]phenyl]methyl]pyridazin-3-one；6-(1-methylpyrazol-4-yl)-2-[[3-[[4-(1-methylpyrazol-4-yl)pyrimidin-2-yl]amino]phenyl]methyl]pyridazin-3-one
• 化学式: C₂₃H₂₁N₉O
• 分子量: 439.479
• InChiKey: ZPPSZAJURBXEBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(1-甲基吡唑)乙酮 在 铁粉 、 caesium carbonate 、 对甲苯磺酸 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 6-(1-methyl-1H-pyrazol-4-yl)-2-(3-((4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)benzyl)pyridazin-3(2H)-one
  参考文献：
  名称：

  Pyridazinone derivatives displaying highly potent and selective inhibitory activities against c-Met tyrosine kinase

  摘要：

  Over activation of c-Met tyrosine kinase is known to promote tumorigenesis and metastasis, as well as to cause therapeutic resistance. Herein we describe the design, synthesis and biological activities of novel, ATP-competitive, c-Met tyrosine kinase inhibitors that are members of the 6-aryl-2-(3-(heteroarylamino) benzyl)pyridazinone family. A structure-activity relationship (SAR) study of these substances led to identification of pyridazinone 19 as a highly selective and potent c-Met tyrosine inhibitor, which displays favorable pharmacokinetic properties in mice and significant antitumor activity against a c-Met driven EBC-1 tumor xenograft. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.042

文献信息

• Pyridazinone derivatives displaying highly potent and selective inhibitory activities against c-Met tyrosine kinase
  作者：Yang Liu、Shiyu Jin、Xia Peng、Dong Lu、Limin Zeng、Yiming Sun、Jing Ai、Meiyu Geng、Youhong Hu

  DOI：10.1016/j.ejmech.2015.11.042

  日期：2016.1

  Over activation of c-Met tyrosine kinase is known to promote tumorigenesis and metastasis, as well as to cause therapeutic resistance. Herein we describe the design, synthesis and biological activities of novel, ATP-competitive, c-Met tyrosine kinase inhibitors that are members of the 6-aryl-2-(3-(heteroarylamino) benzyl)pyridazinone family. A structure-activity relationship (SAR) study of these substances led to identification of pyridazinone 19 as a highly selective and potent c-Met tyrosine inhibitor, which displays favorable pharmacokinetic properties in mice and significant antitumor activity against a c-Met driven EBC-1 tumor xenograft. (C) 2015 Elsevier Masson SAS. All rights reserved.