4-(2-(5-chloro-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)-acetamido)-N-(methylsulfonyl)benzamide

• 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: 4-(2-(5-chloro-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)-acetamido)-N-(methylsulfonyl)benzamide
• 英文别名: 4-[[2-(5-chloro-2-oxo-1,3-benzothiazol-3-yl)acetyl]amino]-N-methylsulfonylbenzamide
• 化学式: C₁₇H₁₄ClN₃O₅S₂
• 分子量: 439.9
• InChiKey: UBSSUXIQWAFWFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (5-氯-2-氧代-1,3-苯并噻唑-3(2H)-基)乙酸 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-(2-(5-chloro-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)-acetamido)-N-(methylsulfonyl)benzamide
  参考文献：
  名称：

  Structure-Based Development of a Protein–Protein Interaction Inhibitor Targeting Tumor Necrosis Factor Receptor-Associated Factor 6

  摘要：

  The interactions between tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and TNF superfamily receptors (TNFRSFs) are promising targets for rheumatoid arthritis (RA) treatment. However, due to the challenging nature of protein-protein interactions (PPIs), a potent inhibitor that surpasses the affinity of the TRAF6-TNFRSF interactions has not been developed. We developed a small-molecule PPI inhibitor of TRAF6-TNFRSF interactions using NMR and in silico techniques. The most potent compound, TRI4, exhibited an affinity higher than those of TNFRSFs and competitively inhibited a TRAF6-TNFRSF interaction. Structural characterization of the TRAF6-TRI4 complex revealed that TRI4 supplants key interactions in the TRAF6-TNFRSF interfaces. In addition, some TRAF6-TRI4 interactions extend beyond the TRAF6-TNFRSF interfaces and increase the binding affinity. Our successful development of TRI4 provides a new Opportunity for RA treatment and implications fur structure-guided development of PPI inhibitors.

  DOI：

  10.1021/acs.jmedchem.5b00778