2-(N-methylindol-3-ylmethylene)-4,6-dihydroxybenzofuran-3(2H)-one | 1228017-22-8

• 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-(N-methylindol-3-ylmethylene)-4,6-dihydroxybenzofuran-3(2H)-one
• 英文别名: 4,6-dihydroxy-2-[(1-methylindol-3-yl)methylidene]-1-benzofuran-3-one
• CAS: 1228017-22-8
• 化学式: C₁₈H₁₃NO₄
• 分子量: 307.306
• InChiKey: IBKQDXXHRSSNHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.21
• 重原子数：
  23.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  71.69
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  间苯三酚 在 盐酸 、 水 、 potassium hydroxide 、 zinc(II) chloride 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 反应 8.0h， 生成 2-(N-methylindol-3-ylmethylene)-4,6-dihydroxybenzofuran-3(2H)-one
  参考文献：
  名称：

  B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase

  摘要：

  Following our recent report showing the potential of naturally occurring aurones (2-benzylidenebenzofuran-3(2H)-ones) as anti-hepatitis C virus (HCV) agents, efforts were continued in order to refine the structural requirements for the inhibitory effect on HCV RNA-dependent RNA polymerase (RdRp). In this study, we targeted the B-ring moiety of aurones with the aim to improve structural features associated with higher inhibition of the targeted polymerase. In vitro evaluation of the RdRp inhibitory activity of the 37 newly synthesized compounds pointed out that the replacement of the B-ring with an N-substituted indole moiety induced the highest inhibitory effect. Of these, compounds 31, 40 and 41 were found to be the most active (IC50 = 2.3-2.4 μM). Docking experiments performed with the most active compounds revealed that the allosteric thumb pocket I of RdRp is the binding pocket for aurone analogues.

  DOI：

  10.1016/j.ejmech.2014.04.005

文献信息

• Novel benzofuran-3-one indole inhibitors of PI3 kinase-α and the mammalian target of rapamycin: Hit to lead studies
  作者：Matthew G. Bursavich、Natasja Brooijmans、Lawrence Feldberg、Irwin Hollander、Stephen Kim、Sabrina Lombardi、Kaapjoo Park、Robert Mallon、Adam M. Gilbert

  DOI：10.1016/j.bmcl.2010.02.082

  日期：2010.4

  A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) inhibitors identified via HTS has been prepared. The optimized inhibitors possess single digit nanomolar activity against p110 alpha (PI3K-alpha), good pharmaceutical properties, selectivity versus p110 gamma (PI3K-gamma), and tunable selectivity versus the mammalian target of rapamycin ( mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-alpha and mTOR supports the proposed rationale for selectivity. Compounds show activity in multiple cellular proliferation assays with signaling through the PI3K pathway confirmed via phospho-Akt inhibition in PC-3 cells. (C) 2010 Elsevier Ltd. All rights reserved.