2-amino-N-butyl-5-ethylthiophene-3-carboxamide | 1418733-72-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2-amino-N-butyl-5-ethylthiophene-3-carboxamide
• CAS: 1418733-72-8
• 化学式: C₁₁H₁₈N₂OS
• 分子量: 226.343
• InChiKey: SOHPQRQTUFEUDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  83.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-硝基-2-糠酰氯 、 2-amino-N-butyl-5-ethylthiophene-3-carboxamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以114 mg的产率得到N-[3-(butylcarbamoyl)-5-ethylthiophen-2-yl]-5-nitrofuran-2-carboxamide
  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
• 作为产物：
  描述：

  丙醛 、 正丁基-2-氰基乙酰胺 在 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 三乙胺 作用下， 以 乙醇 为溶剂， 以30%的产率得到2-amino-N-butyl-5-ethylthiophene-3-carboxamide
  参考文献：
  名称：

  Design of a novel thiophene inhibitor of 15-lipoxygenase-1 with both anti-inflammatory and neuroprotective properties

  摘要：

  The enzyme 15-lipoxygenase-1 (15-LOX-1) plays a dual role in diseases with an inflammatory component. On one hand 15-LOX-1 plays a role in pro-inflammatory gene expression and on the other hand it has been shown to be involved in central nervous system (CNS) disorders by its ability to mediate oxidative stress and damage of mitochondrial membranes under hypoxic conditions. In order to further explore applications in the CNS, novel 15-LOX-1 inhibitors with favorable physicochemical properties need to be developed. Here, we present Substitution Oriented Screening (SOS) in combination with Multi Component Chemistry (MCR) as an "effective strategy to identify a diversely substituted small heterocyclic inhibitors for 15-LOX-1, denoted ThioLox, with physicochemical properties superior to previously identified inhibitors. Ex vivo biological evaluation in precision-cut lung slices (PCLS) showed inhibition of pro-inflammatory gene expression and in vitro studies on neuronal HT-22 cells showed a strong protection against glutamate toxicity for this 15-LOX-1 inhibitor. This provides a novel approach to identify novel small with favorable physicochemical properties for exploring 15-LOX-1 as a drug target in inflammatory diseases and neurodegeneration. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.07.010