3-acetyl-5,7-dimethoxyindole

• 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: 3-acetyl-5,7-dimethoxyindole
• 英文别名: 3-acetyl-5,7-dimethoxy-1H-indole；1-(5,7-dimethoxy-1H-indol-3-yl)ethanone
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: AGMFPJYBNYWDOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-acetyl-5,7-dimethoxyindole 在 水 、 sodium methylate 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.64h， 生成 4-[1-(4-fluorobenzyl)-5,7-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid
  参考文献：
  名称：

  HIV-1 integrase strand-transfer inhibitors: Design, synthesis and molecular modeling investigation

  摘要：

  This study is focused on a new series of benzylindole derivatives with various substituents at the benzene-fused ring, suggested by our 3D pharmacophore model developed for HIV-1 integrase inhibitors (INIs). All synthesized compounds proved to be active in the nanomolar range (6-35 nM) on the strand-transfer step (ST). In particular, derivative 4-[1-(4-fluorobenzyl)-5,7-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (8e), presenting the highest best-fit value on pharmacophore model, showed a potency comparable to that of clinical INSTIs GS 9137 (1) and MK-0518 (2). The binding mode of our molecules has been investigated using the recently published crystal structure of the complex of full-length integrase from the prototype foamy virus in complex with its cognate DNA (PFV-IN/DNA). The results highlighted the ability of derivative Se to assume the same binding mode of MK-0518 and GS 9137. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.12.012
• 作为产物：
  描述：

  3,5-dimethoxy-β-nitrostyrene 在 乙酸酐 、 copper(II) nitrate 、 溶剂黄146 、 三氯氧磷 作用下， 反应 2.0h， 生成 3-acetyl-5,7-dimethoxyindole
  参考文献：
  名称：

  Regioselective reactivity of some 5,7-dimethoxyindoles

  摘要：

  The reactivity of some 5,7-dimethoxyindoles with respect to electrophiles has been investigated. The favoured sites for reaction are C3 and C4 and regioselectivity can be controlled by the judicious arrangement of electron-withdrawing substituents. Results of formylation, acylation, the Mannich reaction, bromination and nitration are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.03.048

文献信息

• Regioselective reactivity of some 5,7-dimethoxyindoles
  作者：Glenn C. Condie、Michelle F. Channon、Andrew J. Ivory、Naresh Kumar、David StC. Black

  DOI：10.1016/j.tet.2005.03.048

  日期：2005.5

  The reactivity of some 5,7-dimethoxyindoles with respect to electrophiles has been investigated. The favoured sites for reaction are C3 and C4 and regioselectivity can be controlled by the judicious arrangement of electron-withdrawing substituents. Results of formylation, acylation, the Mannich reaction, bromination and nitration are described. (c) 2005 Elsevier Ltd. All rights reserved.
• HIV-1 integrase strand-transfer inhibitors: Design, synthesis and molecular modeling investigation
  作者：Laura De Luca、Sara De Grazia、Stefania Ferro、Rosaria Gitto、Frauke Christ、Zeger Debyser、Alba Chimirri

  DOI：10.1016/j.ejmech.2010.12.012

  日期：2011.2

  This study is focused on a new series of benzylindole derivatives with various substituents at the benzene-fused ring, suggested by our 3D pharmacophore model developed for HIV-1 integrase inhibitors (INIs). All synthesized compounds proved to be active in the nanomolar range (6-35 nM) on the strand-transfer step (ST). In particular, derivative 4-[1-(4-fluorobenzyl)-5,7-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (8e), presenting the highest best-fit value on pharmacophore model, showed a potency comparable to that of clinical INSTIs GS 9137 (1) and MK-0518 (2). The binding mode of our molecules has been investigated using the recently published crystal structure of the complex of full-length integrase from the prototype foamy virus in complex with its cognate DNA (PFV-IN/DNA). The results highlighted the ability of derivative Se to assume the same binding mode of MK-0518 and GS 9137. (C) 2010 Elsevier Masson SAS. All rights reserved.