4-(5-hydroxy-1,3-dimethyl-1H-indol-2-yl)benzene-1,2-diol | 1610763-45-5

• 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: 4-(5-hydroxy-1,3-dimethyl-1H-indol-2-yl)benzene-1,2-diol
• 英文别名: 4-(5-Hydroxy-1,3-dimethylindol-2-yl)benzene-1,2-diol；4-(5-hydroxy-1,3-dimethylindol-2-yl)benzene-1,2-diol
• CAS: 1610763-45-5
• 化学式: C₁₆H₁₅NO₃
• 分子量: 269.3
• InChiKey: IZVIQXAULWLTNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  65.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(3,4-bis(benzyloxy)phenyl)-3-methyl-1H-indol-5-ol 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 36.0h， 生成 4-(5-hydroxy-1,3-dimethyl-1H-indol-2-yl)benzene-1,2-diol
  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

文献信息

• Synthesis, Antiproliferative Effect, and Topoisomerase II Inhibitory Activity of 3-Methyl-2-phenyl-1<i>H</i>-indoles
  作者：Nace Zidar、Daniela Secci、Tihomir Tomašič、Lucija Peterlin Mašič、Danijel Kikelj、Daniele Passarella、Aida Nelly Garcia Argaez、Mariafrancesca Hyeraci、Lisa Dalla Via

  DOI：10.1021/acsmedchemlett.9b00557

  日期：2020.5.14

  investigated for antiproliferative activity on three human tumor cell lines, HeLa, A2780, and MSTO-211H, and some structure-activity relationships were drawn up. The GI50 values of the most potent compounds (32 and 33) were lower than 5 μM in all tested cell lines. For the most biologically relevant derivatives, the effect on human DNA topoisomerase II relaxation activity was investigated, which highlighted

  制备了一系列3-甲基-2-苯基-1H-吲哚，并研究了其对三种人类肿瘤细胞HeLa，A2780和MSTO-211H的抗增殖活性，并绘制了一些构效关系。在所有测试的细胞系中，最有效的化合物（32和33）的GI50值均低于5μM。对于生物学上最相关的衍生物，研究了其对人DNA拓扑异构酶II松弛活性的影响，突出了抗增殖作用与拓扑异构酶II抑制之间的良好相关性。已显示最有效的衍生物32诱导凋亡途径。所获得的结果突出了3-甲基-2-苯基-1H-吲哚作为有前途的支架，用于进一步优化具有有效的抗增殖和抗拓扑异构酶II活性的化合物。
• Bazedoxifene-Scaffold-Based Mimetics of Solomonsterols A and B as Novel Pregnane X Receptor Antagonists
  作者：Žiga Hodnik、Lucija Peterlin Mašič、Tihomir Tomašić、Domen Smodiš、Claudio D’Amore、Stefano Fiorucci、Danijel Kikelj

  DOI：10.1021/jm500351m

  日期：2014.6.12

  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.