N-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-3-(4-fluorophenyl)-1-methyl-1H-indole-2-carboxamide | 1450743-00-6

• 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-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-3-(4-fluorophenyl)-1-methyl-1H-indole-2-carboxamide
• 英文别名: N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-3-(4-fluorophenyl)-1-methylindole-2-carboxamide
• CAS: 1450743-00-6
• 化学式: C₂₇H₂₆Cl₂FN₃O
• 分子量: 498.427
• InChiKey: ATVQAQMGOFUZJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  28.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl 3-bromo-1-methyl-1H-indole-2-carboxylate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 N-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-3-(4-fluorophenyl)-1-methyl-1H-indole-2-carboxamide
  参考文献：
  名称：

  Synthetic studies of centromere-associated protein-E (CENP-E) inhibitors: 1.Exploration of fused bicyclic core scaffolds using electrostatic potential map

  摘要：

  Centromere-associated protein-E (CENP-E), a mitotic kinesin that plays an important role in mitotic progression, is an attractive target for cancer therapeutic drugs. For the purpose of developing novel CENP-E inhibitors as cancer therapeutics, we investigated a fused bicyclic compound identified by high throughput screening, 4-oxo-4,5-dihydrothieno[3,4-clpyridine-6-carboxamide la. Based on this scaffold, we designed inhibitors for efficient binding at the L5 site in CENP-E utilizing homology modeling as well as electrostatic potential map (EPM) analysis to enhance CENP-E inhibitory activity. This resulted in a new lead, 5-bromoimidazo[l,2-a]pyridine 7, which showed potent CENP-E enzyme inhibition (IC50: 50 nM) and cellular activity with accumulation of phosphorylated histone H3 in HeLa cells. Our homology model and EPM analysis proved to be useful tools for the rational design of CENP-E inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.067

文献信息

• Synthetic studies of centromere-associated protein-E (CENP-E) inhibitors: 1.Exploration of fused bicyclic core scaffolds using electrostatic potential map
  作者：Takaharu Hirayama、Masanori Okaniwa、Takashi Imada、Akihiro Ohashi、Momoko Ohori、Kenichi Iwai、Kouji Mori、Tomohiro Kawamoto、Akihiro Yokota、Toshimasa Tanaka、Tomoyasu Ishikawa

  DOI：10.1016/j.bmc.2013.05.067

  日期：2013.9

  Centromere-associated protein-E (CENP-E), a mitotic kinesin that plays an important role in mitotic progression, is an attractive target for cancer therapeutic drugs. For the purpose of developing novel CENP-E inhibitors as cancer therapeutics, we investigated a fused bicyclic compound identified by high throughput screening, 4-oxo-4,5-dihydrothieno[3,4-clpyridine-6-carboxamide la. Based on this scaffold, we designed inhibitors for efficient binding at the L5 site in CENP-E utilizing homology modeling as well as electrostatic potential map (EPM) analysis to enhance CENP-E inhibitory activity. This resulted in a new lead, 5-bromoimidazo[l,2-a]pyridine 7, which showed potent CENP-E enzyme inhibition (IC50: 50 nM) and cellular activity with accumulation of phosphorylated histone H3 in HeLa cells. Our homology model and EPM analysis proved to be useful tools for the rational design of CENP-E inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.