Ethyl 2-[(5-nitrofuran-2-carbonyl)amino]thiophene-3-carboxylate | 908502-60-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: Ethyl 2-[(5-nitrofuran-2-carbonyl)amino]thiophene-3-carboxylate
• CAS: 908502-60-3
• 化学式: C₁₂H₁₀N₂O₆S
• 分子量: 310.287
• InChiKey: XMLZULDAJZRLBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-硝基-2-糠酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 Ethyl 2-[(5-nitrofuran-2-carbonyl)amino]thiophene-3-carboxylate
  参考文献：
  名称：

  A Class of 5-Nitro-2-furancarboxylamides with Potent Trypanocidal Activity against Trypanosoma brucei in Vitro

  摘要：

  Recently, the World Health Organization approved the nifurtimox-eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, similar to 1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human He La cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.

  DOI：

  10.1021/jm301215e

文献信息

• A Class of 5-Nitro-2-furancarboxylamides with Potent Trypanocidal Activity against <i>Trypanosoma brucei</i> in Vitro
  作者：Linna Zhou、Gavin Stewart、Emeline Rideau、Nicholas J. Westwood、Terry K. Smith

  DOI：10.1021/jm301215e

  日期：2013.2.14

  Recently, the World Health Organization approved the nifurtimox-eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, similar to 1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human He La cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.