2-((2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-5-yl)oxy)ethyl acetate | 1610763-28-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-((2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-5-yl)oxy)ethyl acetate
• CAS: 1610763-28-4
• 化学式: C₂₆H₂₅NO₄
• 分子量: 415.489
• InChiKey: VZXGDENDZRCEBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.66
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  60.55
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-((2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-5-yl)oxy)ethyl acetate 在 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以85%的产率得到2-((2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-5-yl)oxy)ethanol
  参考文献：
  名称：

  Bazedoxifene-Scaffold-Based Mimetics of Solomonsterols A and B as Novel Pregnane X Receptor Antagonists

  摘要：

  Pregnane X receptor (PXR), a member of the NR1I nuclear receptor family, acts as a xenobiotic sensor and a paramount transcriptional regulator of drug-metabolizing enzymes and transporters. The overexpression of PXR in various cancer cells indicates the importance of PXR as a drug target for countering multidrug resistance in anticancer treatments. We describe the discovery of novel bazedoxifene-scaffold-based PXR antagonists inspired by the marine sulfated steroids solomonsterol A and B as natural leads. A luciferase reporter assay on a PXR-transfected HepG2 cell line identified compounds 19-24 as promising PXR antagonists. Further structure-activity relationship studies of the most active PXR antagonist from the series (compound 20, IC50 = 11 mu M) revealed the importance of hydroxyl groups as hydrogen-bond donors for PXR antagonistic activity. PXR antagonists 20 and 24 (IC50 = 14 mu M), in addition to the downregulation of PXR expression, exhibited inhibition of PXR-induced CYP3A4 expression, which illustrates their potential to suppress PXR-regulated phase-I drug metabolism.

  DOI：

  10.1021/jm500351m
• 作为产物：
  描述：

  4'-苯甲氧基-2-溴苯丙酮 在 4-(methoxymethoxy)benzenaminium chloride 、 caesium carbonate 、 三乙胺 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 50.0h， 生成 2-((2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-5-yl)oxy)ethyl acetate
  参考文献：
  名称：

  Bazedoxifene-Scaffold-Based Mimetics of Solomonsterols A and B as Novel Pregnane X Receptor Antagonists

  摘要：

  Pregnane X receptor (PXR), a member of the NR1I nuclear receptor family, acts as a xenobiotic sensor and a paramount transcriptional regulator of drug-metabolizing enzymes and transporters. The overexpression of PXR in various cancer cells indicates the importance of PXR as a drug target for countering multidrug resistance in anticancer treatments. We describe the discovery of novel bazedoxifene-scaffold-based PXR antagonists inspired by the marine sulfated steroids solomonsterol A and B as natural leads. A luciferase reporter assay on a PXR-transfected HepG2 cell line identified compounds 19-24 as promising PXR antagonists. Further structure-activity relationship studies of the most active PXR antagonist from the series (compound 20, IC50 = 11 mu M) revealed the importance of hydroxyl groups as hydrogen-bond donors for PXR antagonistic activity. PXR antagonists 20 and 24 (IC50 = 14 mu M), in addition to the downregulation of PXR expression, exhibited inhibition of PXR-induced CYP3A4 expression, which illustrates their potential to suppress PXR-regulated phase-I drug metabolism.

  DOI：

  10.1021/jm500351m