1-(4-(benzyloxy)phenyl)-2-((4-(methoxymethoxy)phenyl)amino)propan-1-one | 1610763-22-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(benzyloxy)phenyl)-2-((4-(methoxymethoxy)phenyl)amino)propan-1-one
• CAS: 1610763-22-8
• 化学式: C₂₄H₂₅NO₄
• 分子量: 391.467
• InChiKey: YVLNXMSJOAEHQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.93
• 重原子数：
  29.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  56.79
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-(4-(benzyloxy)phenyl)-2-((4-(methoxymethoxy)phenyl)amino)propan-1-one 在 palladium 10% on activated carbon 、 4-(methoxymethoxy)benzenaminium chloride 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 29.0h， 生成 3-甲基-5-羟基-2-(4-羟基苯基)-1H-吲哚
  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‘-苄氧基苯丙酮 在 溴 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 16.5h， 生成 1-(4-(benzyloxy)phenyl)-2-((4-(methoxymethoxy)phenyl)amino)propan-1-one
  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