3-acetyl-4,5-dimethoxy-1H-indole | 1269920-04-8

• 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: 3-acetyl-4,5-dimethoxy-1H-indole
• 英文别名: 1-(4,5-dimethoxy-1H-indol-3-yl)ethanone
• CAS: 1269920-04-8
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: GNFQLDPAFJGLFV-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-4,5-dimethoxy-1H-indole 在 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.14h， 生成 ethyl 4-[1-(4-fluorobenzyl)-4,5-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate
  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：

  2,3-dimethoxy-6,β-dinitrostyrene 在 silica gel 、 铁粉 、 溶剂黄146 、 三氯氧磷 作用下， 反应 13.0h， 生成 3-acetyl-4,5-dimethoxy-1H-indole
  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

文献信息

• Synthesis, biological screening and ADME prediction of benzylindole derivatives as novel anti-HIV-1, anti-fungal and anti-bacterial agents
  作者：A. M. Kashid、P. N. Dube、P. G. Alkutkar、K. G. Bothara、S. N. Mokale、S. C. Dhawale

  DOI：10.1007/s00044-012-0463-6

  日期：2013.10

  Present study is focused on design, synthesis, and biological evaluation of substituted benzylindole derivatives as anti-HIV, anti-fungal, and anti-bacterial agents. Out of the reported compounds, compound B1 and B2 showed potent Anti-HIV activity, whereas compound B1–B4 showed good anti-fungal and anti-bacterial activity. ADME properties of benzylindol analogs were analyzed using Qikprop 2.5 tool

  目前的研究集中在取代，取代的吲哚衍生物作为抗HIV，抗真菌和抗菌剂的设计，合成和生物学评估上。在报告的化合物中，化合物B1和B2显示出有效的抗HIV活性，而化合物B1 - B4显示出良好的抗真菌和抗菌活性。使用Schrodinger的Qikprop 2.5工具分析苄基吲哚类似物的ADME性质。
• 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.