2-(4-Chlorophenyl)sulfonyl-3-methylsulfanyl-3-[3-(trifluoromethyl)anilino]prop-2-enenitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-Chlorophenyl)sulfonyl-3-methylsulfanyl-3-[3-(trifluoromethyl)anilino]prop-2-enenitrile
• 化学式: C₁₇H₁₂ClF₃N₂O₂S₂
• 分子量: 432.875
• InChiKey: OIDZPEDDRCNOLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (4-氯苯基硫)乙腈 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 6.0h， 生成 2-(4-Chlorophenyl)sulfonyl-3-methylsulfanyl-3-[3-(trifluoromethyl)anilino]prop-2-enenitrile
  参考文献：
  名称：

  Inhibitors of the Diadenosine Tetraphosphate Phosphorylase Rv2613c of Mycobacterium tuberculosis

  摘要：

  The intracellular concentration of diadenosine tetraphospate (Ap(4)A) increases upon exposure to stress conditions. Despite being discovered over 50 years ago, the cellular functions of Ap(4)A are still enigmatic. If and how the varied Ap(4)A is a signal and involved in the signaling pathways leading to an appropriate cellular response remain to be discovered. Because the turnover of Ap(4)A by Ap(4)A cleaving enzymes is rapid, small molecule inhibitors for these enzymes would provide tools for the more detailed study of the role of Ap(4)A. Here, we describe the development of a high-throughput screening assay based on a fluorogenic Ap(4)A substrate for the identification and optimization of small molecule inhibitors for Ap(4)A cleaving enzymes. As proof-of-concept we screened a library of over 42 000 compounds toward their inhibitory activity against the Ap(4)A phosphorylase (Rv2613c) of Mycobacterium tuberculosis (Mtb). A sulfanylacrylonitril derivative with an IC50 of 260 +/- 50 nM in vitro was identified. Multiple derivatives were synthesized to further optimize their properties with respect to their in vitro IC50 values and their cytotoxicity against human cells (HeLa). In addition, we selected two hits to study their antimycobacterial activity against virulent Mtb to show that they might be candidates for further development of antimycobacterial agents against multidrug-resistant Mtb.

  DOI：

  10.1021/acschembio.7b00653