2-[2-Amino-5-(1-ethylindol-5-yl)pyrimidin-4-yl]-5-methoxyphenol | 1289141-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-[2-Amino-5-(1-ethylindol-5-yl)pyrimidin-4-yl]-5-methoxyphenol
• 英文别名: 2-[2-amino-5-(1-ethylindol-5-yl)pyrimidin-4-yl]-5-methoxyphenol
• CAS: 1289141-86-1
• 化学式: C₂₁H₂₀N₄O₂
• 分子量: 360.415
• InChiKey: KBLISKGVJDOEKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴-1-乙基-1H-吲哚 在 正丁基锂 、 palladium 10% on activated carbon 、 potassium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 10.0h， 生成 2-[2-Amino-5-(1-ethylindol-5-yl)pyrimidin-4-yl]-5-methoxyphenol
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors

  摘要：

  Members of a series of 2,4,5-substituted pyrimidine derivatives were synthesized, and their interactions with tubulin and their antiproliferative activities against the human hepatocellular carcinoma cells of liver (BEL-7402) were evaluated. One member of this family, the indole-pyrimidine 4k, having an indole-aryl-substituted aminopyrimidine structure, was observed to be an excellent inhibitor of tubulin polymerization (IC50 = 0.79 mu M) and to display significantly high antiproliferative activities against several cancer cell lines with IC50 values ranging from 16 to 62 nM. This substance displayed a high propensity to arrests cells at the G(2)/M phase of the cell cycle (EC50 = 20 nM). In addition, 4k was found to competitively inhibit colchicine binding to tubulin, indicating that it binds to the colchicine-binding site of tubulin. The observations made in this investigation demonstrate that 2,4,5-substituted pyrimidines represent a new class of tubulin polymerization inhibitors with significant antiproliferative activity.

  DOI：

  10.1021/jm101388d

文献信息

• Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors
  作者：Fuchun Xie、Hongbing Zhao、Dewen Li、Hong Chen、Haitian Quan、Xiaojing Shi、Liguang Lou、Youhong Hu

  DOI：10.1021/jm101388d

  日期：2011.5.12

  Members of a series of 2,4,5-substituted pyrimidine derivatives were synthesized, and their interactions with tubulin and their antiproliferative activities against the human hepatocellular carcinoma cells of liver (BEL-7402) were evaluated. One member of this family, the indole-pyrimidine 4k, having an indole-aryl-substituted aminopyrimidine structure, was observed to be an excellent inhibitor of tubulin polymerization (IC50 = 0.79 mu M) and to display significantly high antiproliferative activities against several cancer cell lines with IC50 values ranging from 16 to 62 nM. This substance displayed a high propensity to arrests cells at the G(2)/M phase of the cell cycle (EC50 = 20 nM). In addition, 4k was found to competitively inhibit colchicine binding to tubulin, indicating that it binds to the colchicine-binding site of tubulin. The observations made in this investigation demonstrate that 2,4,5-substituted pyrimidines represent a new class of tubulin polymerization inhibitors with significant antiproliferative activity.