methyl 2-((2-(3,4,5-trimethoxyphenylamino)imidazo[1,2-a][1,3,5]triazin-4-yl)methyl)benzoate

• 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: methyl 2-((2-(3,4,5-trimethoxyphenylamino)imidazo[1,2-a][1,3,5]triazin-4-yl)methyl)benzoate
• 英文别名: Methyl 2-[[2-(3,4,5-trimethoxyanilino)imidazo[1,2-a][1,3,5]triazin-4-yl]methyl]benzoate；methyl 2-[[2-(3,4,5-trimethoxyanilino)imidazo[1,2-a][1,3,5]triazin-4-yl]methyl]benzoate
• 化学式: C₂₃H₂₃N₅O₅
• 分子量: 449.466
• InChiKey: AKHBGUNLVCLWFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 2-((2-(3,4,5-trimethoxyphenylamino)imidazo[1,2-a][1,3,5]triazin-4-yl)methyl)benzoate 、 甲胺 在 ammonium hydroxide 作用下， 以 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 0.25h， 以64%的产率得到N-methyl-2-((2-(3,4,5-trimethoxyphenylamino)imidazo[1,2-a][1,3,5]triazin-4-yl)methyl)benzamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Imidazo[1,2-a][1,3,5]triazines and Their Derivatives as Focal Adhesion Kinase Inhibitors with Antitumor Activity

  摘要：

  A series of triazinic inhibitors of focal adhesion kinase (FAK) have been recently shown to exert antiangiogenic activity against HUVEC cells and anticancer efficacy against several cancer cell lines. We report herein that we further explored the heterocyclic core of these inhibitors by a fused imidazole ring with the triazine to provide imidazo[1,2-a][1,3,5]triazines. Importantly, these new compounds displayed 10(-7-)10(-8) M IC50 values, and the best inhibitor showed IC50 value of 50 nM against FAK enzymatic activity. Several inhibitors potently inhibited the proliferation of a panel of cancer cell lines expressing high levels of FAK. Apoptosis analysis in U87-MG and HCT-116 cell lines suggested that these compounds delayed cell cycle progression by arresting cells in the G2/M phase of the cell cycle, retarding cell growth. Further investigation demonstrated that these compounds strongly inhibited cell-matrix adhesion, migration, and invasion of U87-MG cells.

  DOI：

  10.1021/jm500784e
• 作为产物：
  描述：

  3,4,5-trimethoxyphenylbiguanide 在 sodium methylate 作用下， 以 四氢呋喃 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 0.33h， 生成 methyl 2-((2-(3,4,5-trimethoxyphenylamino)imidazo[1,2-a][1,3,5]triazin-4-yl)methyl)benzoate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Imidazo[1,2-a][1,3,5]triazines and Their Derivatives as Focal Adhesion Kinase Inhibitors with Antitumor Activity

  摘要：

  A series of triazinic inhibitors of focal adhesion kinase (FAK) have been recently shown to exert antiangiogenic activity against HUVEC cells and anticancer efficacy against several cancer cell lines. We report herein that we further explored the heterocyclic core of these inhibitors by a fused imidazole ring with the triazine to provide imidazo[1,2-a][1,3,5]triazines. Importantly, these new compounds displayed 10(-7-)10(-8) M IC50 values, and the best inhibitor showed IC50 value of 50 nM against FAK enzymatic activity. Several inhibitors potently inhibited the proliferation of a panel of cancer cell lines expressing high levels of FAK. Apoptosis analysis in U87-MG and HCT-116 cell lines suggested that these compounds delayed cell cycle progression by arresting cells in the G2/M phase of the cell cycle, retarding cell growth. Further investigation demonstrated that these compounds strongly inhibited cell-matrix adhesion, migration, and invasion of U87-MG cells.

  DOI：

  10.1021/jm500784e