2-bromo-4-(di-1H-indol-3-ylmethyl)-6-methoxyphenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-bromo-4-(di-1H-indol-3-ylmethyl)-6-methoxyphenol
• 英文别名: 4-[bis(1H-indol-3-yl)methyl]-2-bromo-6-methoxyphenol
• 化学式: C₂₄H₁₉BrN₂O₂
• 分子量: 447.3
• InChiKey: XKGPDBPRCMDFDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  61
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  吲哚 、 5-溴香兰素 在 溶剂黄146 作用下， 以 水 为溶剂， 生成 2-bromo-4-(di-1H-indol-3-ylmethyl)-6-methoxyphenol
  参考文献：
  名称：

  Bis-Indole Derivatives as Dual Nuclear Receptor 4A1 (NR4A1) and NR4A2 Ligands

  摘要：

  Bis-indole derived compounds such as 1,1-bis(3′-indolyl)-1-(3,5-disubstitutedphenyl) methane (DIM-3,5) and the corresponding 4-hydroxyl analogs (DIM8-3,5) are NR4A1 ligands that act as inverse NR4A1 agonists and are potent inhibitors of tumor growth. The high potency of several DIM-3,5 analogs (IC50 < 1 mg/kg/day), coupled with the >60% similarity of the ligand-binding domains (LBDs) of NR4A1 and NR4A2 and the pro-oncogenic activities of both receptors lead us to hypothesize that these compounds may act as dual NR4A1 and NR4A2 ligands. Using a fluorescence binding assay, it was shown that 22 synthetic DIM8-3,5 and DIM-3,5 analogs bound the LBD of NR4A1 and NR4A2 with most KD values in the low µM range. Moreover, the DIM-3,5 and DIM8-3,5 analogs also decreased NR4A1- and NR4A2-dependent transactivation in U87G glioblastoma cells transfected with GAL4-NR4A1 or GAL4-NR4A2 chimeras and a UAS-luciferase reporter gene construct. The DIM-3,5 and DIM8-3,5 analogs were cytotoxic to U87 glioblastoma and RKO colon cancer cells and the DIM-3,5 compounds were more cytotoxic than the DIM8-3,5 compounds. These studies show that both DIM-3,5 and DIM8-3,5 compounds previously identified as NR4A1 ligands bind both NR4A1 and NR4A2 and are dual NR4A1/2 ligands.

  DOI：

  10.3390/biom14030284