N-ethyl-3-hydroxy-4-thioxo-4H-pyran-2-carbothioamide | 1125465-93-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: N-ethyl-3-hydroxy-4-thioxo-4H-pyran-2-carbothioamide
• 英文别名: N-ethyl-3-hydroxy-4-sulfanylidene-4H-pyran-2-carbothioamide；N-ethyl-3-hydroxy-4-sulfanylidenepyran-2-carbothioamide
• CAS: 1125465-93-1
• 化学式: C₈H₉NO₂S₂
• 分子量: 215.297
• InChiKey: DEPPLFWFIKGKDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-ethyl-3-hydroxy-4-oxo-4H-pyran-2-carboxamide 在 tetraphosphorus decasulfide 、 六甲基二硅氧烷 作用下， 以 苯 为溶剂， 反应 2.5h， 以40%的产率得到N-ethyl-3-hydroxy-4-thioxo-4H-pyran-2-carbothioamide
  参考文献：
  名称：

  Thioamide Hydroxypyrothiones Supersede Amide Hydroxypyrothiones in Potency against Anthrax Lethal Factor

  摘要：

  Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematically varied. It was found that hydroxypyrothione ZBGs generate more potent inhibitors than hydroxypyrone ZBGs. Furthermore, coupling the hydroxypyrothione to a backbone group via a thioamide bond improves potency when compared to an amide linker. QM/MM studies show that the thioamide bond in these inhibitors allows for the formation of two additional hydrogen bonds with the protein active site. In both types of hydroxypyrothione compounds, ligand efficiencies of 0.29-0.54 kcal mol(-1) per heavy atom were achieved. The results highlight the need for a better understanding to optimize the interplay between the ZBG, linker, and backbone to get improved LFi.

  DOI：

  10.1021/jm8013212