5-chloro-3-methyl-N-(7,7,9-trimethyl-3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)-1H-indole-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-chloro-3-methyl-N-(7,7,9-trimethyl-3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)-1H-indole-2-carboxamide
• 化学式: C₂₁H₂₆ClN₃O₂S
• 分子量: 419.975
• InChiKey: FKOKUWYOLBKVCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  28.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  65.2
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  5-氯-3-甲基-1H-吲哚-2-羧酸乙酯 在 一水合肼 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 6.0h， 生成 5-chloro-3-methyl-N-(7,7,9-trimethyl-3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  Superior inhibition of influenza virus hemagglutinin-mediated fusion by indole-substituted spirothiazolidinones

  摘要：

  The influenza virus hemagglutinin (HA) mediates membrane fusion after viral entry by endocytosis. The fusion process requires drastic low pH-induced HA refolding and is prevented by arbidol and tert-butylhydroquinone (TBHQ). We here report a class of superior inhibitors with indole-substituted spirothiazolidinone structure. The most active analogue 5f has an EC50 value against influenza A/H3N2 virus of 1 nM and selectivity index of almost 2000. Resistance data and in silico modeling indicate that 5f combines optimized fitting in the TBHQ/arbidol HA binding pocket with a capability for endosomal accumulation. Both criteria appear relevant to achieve superior inhibitors of HA-mediated fusion.

  DOI：

  10.1016/j.bmc.2019.115130

文献信息

• Superior inhibition of influenza virus hemagglutinin-mediated fusion by indole-substituted spirothiazolidinones
  作者：Gökçe Cihan-Üstündağ、Muhammet Zopun、Evelien Vanderlinden、Elif Ozkirimli、Leentje Persoons、Gültaze Çapan、Lieve Naesens

  DOI：10.1016/j.bmc.2019.115130

  日期：2020.1

  The influenza virus hemagglutinin (HA) mediates membrane fusion after viral entry by endocytosis. The fusion process requires drastic low pH-induced HA refolding and is prevented by arbidol and tert-butylhydroquinone (TBHQ). We here report a class of superior inhibitors with indole-substituted spirothiazolidinone structure. The most active analogue 5f has an EC50 value against influenza A/H3N2 virus of 1 nM and selectivity index of almost 2000. Resistance data and in silico modeling indicate that 5f combines optimized fitting in the TBHQ/arbidol HA binding pocket with a capability for endosomal accumulation. Both criteria appear relevant to achieve superior inhibitors of HA-mediated fusion.