N-ethyl-1-methyl-1H-indole-5-carboxamide

• 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: N-ethyl-1-methyl-1H-indole-5-carboxamide
• 英文别名: N~5~-ethyl-1-methyl-1H-indole-5-carboxamide；N-ethyl-1-methylindole-5-carboxamide
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: QQYDZZNAXZROPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-ethyl-1-methyl-1H-indole-5-carboxamide 在 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 3-(((2-([1,1'-biphenyl]-4-yl)ethyl)(methyl)amino)methyl)-N-ethyl-1-methyl-1H-indole-5-carboxamide
  参考文献：
  名称：

  Identification of an indol-based multi-target kinase inhibitor through phenotype screening and target fishing using inverse virtual screening approach

  摘要：

  A series of 1,3,5-substituted indole derivatives was prepared to explore the anti-proliferative activity against a panel of human tumour cell lines. A 5-carboxamide derivative (27) emerged as the most potent compound of this series, inhibiting the HeLa cell growth at sub-micromolar concentrations. Target fishing of 27 using a combination of inverse virtual screening (IVS) approach and ligand-based shape similarity study identified the top-ranked targets for 27 as belonging to kinome. These results were further confirmed by in vitro binding assays, leading to the identification of 27 as multi-target kinase inhibitor. The compound 27 was further characterized for its antiproliferative activity by in cell studies, showing a mechanism of action involving modification of the cell cycle, increase in ROS release and caspase 3-expression and decrease in ERK expression. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.066
• 作为产物：
  描述：

  吲哚-5-羧酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 N-ethyl-1-methyl-1H-indole-5-carboxamide
  参考文献：
  名称：

  Identification of an indol-based multi-target kinase inhibitor through phenotype screening and target fishing using inverse virtual screening approach

  摘要：

  A series of 1,3,5-substituted indole derivatives was prepared to explore the anti-proliferative activity against a panel of human tumour cell lines. A 5-carboxamide derivative (27) emerged as the most potent compound of this series, inhibiting the HeLa cell growth at sub-micromolar concentrations. Target fishing of 27 using a combination of inverse virtual screening (IVS) approach and ligand-based shape similarity study identified the top-ranked targets for 27 as belonging to kinome. These results were further confirmed by in vitro binding assays, leading to the identification of 27 as multi-target kinase inhibitor. The compound 27 was further characterized for its antiproliferative activity by in cell studies, showing a mechanism of action involving modification of the cell cycle, increase in ROS release and caspase 3-expression and decrease in ERK expression. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.066

文献信息

• Identification of an indol-based multi-target kinase inhibitor through phenotype screening and target fishing using inverse virtual screening approach
  作者：Carmine Ostacolo、Veronica Di Sarno、Gianluigi Lauro、Giacomo Pepe、Simona Musella、Tania Ciaglia、Vincenzo Vestuto、Giuseppina Autore、Giuseppe Bifulco、Stefania Marzocco、Pietro Campiglia、Isabel M. Gomez-Monterrey、Alessia Bertamino

  DOI：10.1016/j.ejmech.2019.01.066

  日期：2019.4

  A series of 1,3,5-substituted indole derivatives was prepared to explore the anti-proliferative activity against a panel of human tumour cell lines. A 5-carboxamide derivative (27) emerged as the most potent compound of this series, inhibiting the HeLa cell growth at sub-micromolar concentrations. Target fishing of 27 using a combination of inverse virtual screening (IVS) approach and ligand-based shape similarity study identified the top-ranked targets for 27 as belonging to kinome. These results were further confirmed by in vitro binding assays, leading to the identification of 27 as multi-target kinase inhibitor. The compound 27 was further characterized for its antiproliferative activity by in cell studies, showing a mechanism of action involving modification of the cell cycle, increase in ROS release and caspase 3-expression and decrease in ERK expression. (C) 2019 Elsevier Masson SAS. All rights reserved.