3-acetyl-4,5-dimethoxy-1-(4-fluorobenzyl)-1H-indole | 1269920-09-3

• 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-1-(4-fluorobenzyl)-1H-indole
• 英文别名: 1-[1-[(4-Fluorophenyl)methyl]-4,5-dimethoxyindol-3-yl]ethanone
• CAS: 1269920-09-3
• 化学式: C₁₉H₁₈FNO₃
• 分子量: 327.355
• InChiKey: FWIQKZWLFNLWKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  40.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-acetyl-4,5-dimethoxy-1-(4-fluorobenzyl)-1H-indole 在 水 、 sodium methylate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.53h， 生成 4-[1-(4-fluorobenzyl)-4,5-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：

  2,3-dimethoxy-6,β-dinitrostyrene 在 silica gel 、 铁粉 、 sodium hydride 、 溶剂黄146 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.11h， 生成 3-acetyl-4,5-dimethoxy-1-(4-fluorobenzyl)-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

• 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.