3-bromo-N-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-4-(4-fluorophenyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide | 1450743-08-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-bromo-N-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-4-(4-fluorophenyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide
• 英文别名: 3-bromo-N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)thieno[3,2-b]pyrrole-5-carboxamide
• CAS: 1450743-08-4
• 化学式: C₂₄H₂₁BrCl₂FN₃OS
• 分子量: 569.325
• InChiKey: LLZQBQNEWUCTIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  56.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-bromo-N-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-4-(4-fluorophenyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide 在 copper(l) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以39%的产率得到3-chloro-N-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-4-(4-fluorophenyl)-4H-thieno[3,2-b]pyrrole-5-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
• 作为产物：
  描述：

  4-溴-2-噻吩甲醛 在 吡啶 、 sodium ethanolate 、 copper diacetate 、 三乙胺 、 N,N-二异丙基乙胺 、 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 、 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.0h， 生成 3-bromo-N-(3,4-dichlorobenzyl)-N-(2-(dimethylamino)ethyl)-4-(4-fluorophenyl)-4H-thieno[3,2-b]pyrrole-5-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.