4-({[4-(2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridin-4-yl)benzoyl]amino}sulfonyl)benzoic acid | 190833-95-5

• 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: 4-({[4-(2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridin-4-yl)benzoyl]amino}sulfonyl)benzoic acid
• 英文别名: 4-[[4-[3,5-Bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridin-4-yl]benzoyl]sulfamoyl]benzoic acid
• CAS: 190833-95-5
• 化学式: C₂₇H₂₈N₂O₉S
• 分子量: 556.593
• InChiKey: STUXFCUSTKGJPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  174
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Val-Abo-(D,L)-Val-CF₃ 、 4-({[4-(2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridin-4-yl)benzoyl]amino}sulfonyl)benzoic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 4-({[4-(2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridin-4-yl)benzoyl]amino}sulfonyl)benzoyl-Val-Abo-(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the end of the N-terminal side chain and with compounds in which the N-terminal valine of the tripeptidic sequence had been replaced by a epsilon-substituted lysine.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：

  ethyl 4-({[(2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridin-4-yl)benzoyl]amino}sulfonyl)benzoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 20.0h， 生成 4-({[4-(2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridin-4-yl)benzoyl]amino}sulfonyl)benzoic acid
  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