ethyl 3-[({[(4-hydroxy-3,5-di-tert-butylphenyl)thio]acetyl}amino)sulfonyl]-4-chlorobenzoate | 173457-17-5

• 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: ethyl 3-[({[(4-hydroxy-3,5-di-tert-butylphenyl)thio]acetyl}amino)sulfonyl]-4-chlorobenzoate
• 英文别名: Ethyl 4-chloro-3-[[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylacetyl]sulfamoyl]benzoate
• CAS: 173457-17-5
• 化学式: C₂₅H₃₂ClNO₆S₂
• 分子量: 542.117
• InChiKey: WVSSQDMXCFGSDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-[({[(4-hydroxy-3,5-di-tert-butylphenyl)thio]acetyl}amino)sulfonyl]-4-chlorobenzoate 在 4-二甲氨基吡啶 、 sodium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 4-{[({4-chloro-3-[({[(4-hydroxy-3,5-di-tert-butylphenyl)thio]acetyl}amino)sulfonyl]phenyl}carbonyl)amino]sulfonyl}benzoyl-Val-(2S,3aS,7aS)-Phi-(R,S)-Val-CF3
  参考文献：
  名称：

  Dual Inhibition of Human Leukocyte Elastase and Lipid Peroxidation:  In Vitro and in Vivo Activities of Azabicyclo[2.2.2]octane and Perhydroindole Derivatives

  摘要：

  A series of potent and selective human leukocyte elastase (HLE) inhibitors of the Val-Pro-Val type has been developed. Initially, the central proline residue was replaced by nonnatural amino acids Phi ((2S,3aS,7aS)-perhydroindole-2-carboxy acid) and Abo ((3S)-2-azabicyclo[2.2.2]octane-3-carboxylic acid), and secondly several groups able to confer antioxidant properties to the molecule were introduced at the lipophilic N-terminal side chain. When compared to reference inhibitors, in vitro HLE inhibitory potency was maintained (10-100 nM) both with compounds containing the antioxidant moiety at the end of the N-terminal side chain and with compounds in which the N-terminal valine of the tripeptidic sequence had been replaced by a epsilon-substituted lysine. The lipidic peroxidation inhibitory potency of this series of inhibitors was found to be similar to that of the reference antioxidant compounds (around 1 mu M). Moreover, HLE-induced hemorrhage in the hamster lung was effectively prevented (40-60% at 15 mu g/ kg) by most of the inhibitors tested when administered intratracheally 3 h before instillation of elastase. Among the most active analogs, compounds 11a,c,g were still active when administered 18 h before elastase. Interestingly, compound 14a was able to prevent HLE-mediated lung damage when administered 72 h prior to enzymatic challenge, indicating exceptional stability and retention in the lung. Finally, in a 14-day chronic model of emphysema in the hamster, 14a significantly conserved alveolar spaces, a marker of lung tissue destruction, send was more potent; than reference inhibitor ICI 200 880. This indicates that addition of peroxidation inhibitory properties to an HLE inhibitor can provide a powerful in vivo inhibitor of pulmonary tissue destruction.

  DOI：

  10.1021/jm960772z
• 作为产物：
  描述：

  2,6-二叔丁基-4-巯基苯酚 在 4-二甲氨基吡啶 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 ethyl 3-[({[(4-hydroxy-3,5-di-tert-butylphenyl)thio]acetyl}amino)sulfonyl]-4-chlorobenzoate
  参考文献：
  名称：

  Dual Inhibition of Human Leukocyte Elastase and Lipid Peroxidation:  In Vitro and in Vivo Activities of Azabicyclo[2.2.2]octane and Perhydroindole Derivatives

  摘要：

  A series of potent and selective human leukocyte elastase (HLE) inhibitors of the Val-Pro-Val type has been developed. Initially, the central proline residue was replaced by nonnatural amino acids Phi ((2S,3aS,7aS)-perhydroindole-2-carboxy acid) and Abo ((3S)-2-azabicyclo[2.2.2]octane-3-carboxylic acid), and secondly several groups able to confer antioxidant properties to the molecule were introduced at the lipophilic N-terminal side chain. When compared to reference inhibitors, in vitro HLE inhibitory potency was maintained (10-100 nM) both with compounds containing the antioxidant moiety at the end of the N-terminal side chain and with compounds in which the N-terminal valine of the tripeptidic sequence had been replaced by a epsilon-substituted lysine. The lipidic peroxidation inhibitory potency of this series of inhibitors was found to be similar to that of the reference antioxidant compounds (around 1 mu M). Moreover, HLE-induced hemorrhage in the hamster lung was effectively prevented (40-60% at 15 mu g/ kg) by most of the inhibitors tested when administered intratracheally 3 h before instillation of elastase. Among the most active analogs, compounds 11a,c,g were still active when administered 18 h before elastase. Interestingly, compound 14a was able to prevent HLE-mediated lung damage when administered 72 h prior to enzymatic challenge, indicating exceptional stability and retention in the lung. Finally, in a 14-day chronic model of emphysema in the hamster, 14a significantly conserved alveolar spaces, a marker of lung tissue destruction, send was more potent; than reference inhibitor ICI 200 880. This indicates that addition of peroxidation inhibitory properties to an HLE inhibitor can provide a powerful in vivo inhibitor of pulmonary tissue destruction.

  DOI：

  10.1021/jm960772z