4-(5-hydroxy-3-methyl-1H-indol-2-yl)benzene-1,2-diol | 1610763-32-0

• 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-3-methyl-1H-indol-2-yl)benzene-1,2-diol
• CAS: 1610763-32-0
• 化学式: C₁₅H₁₃NO₃
• 分子量: 255.273
• InChiKey: NISNMBUOBIHSCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.5
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(5-hydroxy-3-methyl-1H-indol-2-yl)benzene-1,2-diol 在 吡啶 、 氯磺酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 48.0h， 以65%的产率得到trisodium 4-[3-methyl-5-(sulfonatooxy)-1H-indol-2-yl]benzene-1,2-diyl disulfate
  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：

  苄基(4-羟基苯基)氨基甲酸酯 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 4-(5-hydroxy-3-methyl-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

• Palladium-catalyzed nucleomethylation of alkynes for synthesis of methylated heteroaromatic compounds
  作者：Xi Yang、Gang Wang、Zhi-Shi Ye

  DOI：10.1039/d2sc03294e

  日期：——

  efficient palladium-catalyzed nucleomethylation of alkynes for the simultaneous construction of the heteroaromatic ring and methyl group. The 3-methylindoles, 3-methylbenzofurans and 4-methylisoquinolines were obtained in moderate to excellent yields. Notably, this methodology was employed as a key step for synthesis of a pregnane X receptor antagonist, zindoxifene, bazedoxifene and AFN-1252. The kinetic studies

  在此，我们公开了一种新颖且有效的钯催化炔烃核甲基化，用于同时构建杂芳环和甲基。3-甲基吲哚、3-甲基苯并呋喃和4-甲基异喹啉以中等至优异的产率获得。值得注意的是，该方法被用作合成孕烷 X 受体拮抗剂、津多昔芬、巴多昔芬和 AFN-1252 的关键步骤。动力学研究表明，还原消除可能是决定速率的步骤。
• 一种钯催化炔烃亲核甲基化反应构建甲基杂环化合物的方法
  申请人：大连理工大学

  公开号：CN114907251A

  公开（公告）日：2022-08-16

  本发明公开了一种钯催化炔烃亲核甲基化反应构建甲基杂环化合物的方法。采用三氟醋酸钯/4,5‑双二苯基膦‑9,9‑二甲基氧杂蒽作为催化剂，以邻炔基苯胺，邻炔基苯酚及邻炔基苯亚胺为底物，成功构建了一系列3‑甲基吲哚、4‑甲基异喹啉以及3‑甲基苯并呋喃等甲基杂环化合物，反应最高可获得99％的产率，并以此基础合成了部分含有甲基杂环骨架的药物。本发明操作简便实用，产率好，且催化剂商业可得，反应条件温和，具有潜在的实际应用价值。
• 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.