Ethyl 2-[3-nitro-5-(trifluoromethyl)pyridin-2-yl]acetate | 1211525-07-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: Ethyl 2-[3-nitro-5-(trifluoromethyl)pyridin-2-yl]acetate
• CAS: 1211525-07-3
• 化学式: C₁₀H₉F₃N₂O₄
• 分子量: 278.188
• InChiKey: MYEAFNOUSHSOIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  85
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Ethyl 2-[3-nitro-5-(trifluoromethyl)pyridin-2-yl]acetate 在 铁粉 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-6-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylate
  参考文献：
  名称：

  Lead Optimization of 1,4-Azaindoles as Antimycobacterial Agents

  摘要：

  In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies.

  DOI：

  10.1021/jm500571f
• 作为产物：
  描述：

  Diethyl 2-(3-nitro-5-(trifluoromethyl)pyridin-2-yl)malonate 在 lithium chloride 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成 Ethyl 2-[3-nitro-5-(trifluoromethyl)pyridin-2-yl]acetate
  参考文献：
  名称：

  Lead Optimization of 1,4-Azaindoles as Antimycobacterial Agents

  摘要：

  In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies.

  DOI：

  10.1021/jm500571f