ethyl 5-(3-(dimethylamino)propyl)-7-(4-fluorophenyl)-4-oxo-4,5-dihydrothieno[3,4-c]pyridine-6-carboxylate | 1450742-97-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 5-(3-(dimethylamino)propyl)-7-(4-fluorophenyl)-4-oxo-4,5-dihydrothieno[3,4-c]pyridine-6-carboxylate
• CAS: 1450742-97-8
• 化学式: C₂₁H₂₃FN₂O₃S
• 分子量: 402.49
• InChiKey: FOHFHPUDPAEKJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.0
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51.54
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 5-(3-(dimethylamino)propyl)-7-(4-fluorophenyl)-4-oxo-4,5-dihydrothieno[3,4-c]pyridine-6-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 以100%的产率得到5-(3-(dimethylamino)propyl)-7-(4-fluorophenyl)-4-oxo-4,5-dihydrothieno[3,4-c]pyridine-6-carboxylic acid
  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：

  ethyl 3-(4-((3-(dimethylamino)propyl)carbamoyl)-3-thienyl)-3-(4-fluorophenyl)-2-hydroxyacrylate 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以100%的产率得到ethyl 5-(3-(dimethylamino)propyl)-7-(4-fluorophenyl)-4-oxo-4,5-dihydrothieno[3,4-c]pyridine-6-carboxylate
  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