N-hydroxy-3-{4-[2-(2-methyl-1H-indol-3-yl)ethylsulfamoyl]phenyl}acrylamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: N-hydroxy-3-{4-[2-(2-methyl-1H-indol-3-yl)ethylsulfamoyl]phenyl}acrylamide
• 化学式: C₂₀H₂₁N₃O₄S
• 分子量: 399.47
• InChiKey: JMDMVJXTEMLGRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  111.29
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  1H-2-甲基-3-氨乙基吲哚 在 N-甲基吗啉 、 吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.83h， 生成 N-hydroxy-3-{4-[2-(2-methyl-1H-indol-3-yl)ethylsulfamoyl]phenyl}acrylamide
  参考文献：
  名称：

  Indole-3-ethylsulfamoylphenylacrylamides: Potent histone deacetylase inhibitors with anti-inflammatory activity

  摘要：

  A series of 2-methyl-1H-indol-3-ethylsulfamoylphenylacrylamides based on LBH589-PXD101 core have been synthesized and evaluated for their histone deacetylase (HDAC) inhibitory and anti-inflammatory activity. In vitro, compounds 9-12 show 2.6-fold better HDAC inhibition and 3-fold better IL-6 suppression compared to LBH589.HCl (1.HCl). Furthermore, these compounds did not show apparent cell viability suppression on macrophages while in contrast, treatment with 1.HCl resulted in significant reduction in cell viability as demonstrated by an MTT assay. Repressed expression of iNOS, COX-2 and reduced phosphorylation of p65 revealed the inhibitory effect of these analogues on inflammatory mediator release which is related to inhibited NF-kappa B signals. (N-Hydroxy-3-{3-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide) (9), exhibited ability superior to that of 1.HCl, was able to reduce carrageenan-induced acute inflammation in an animal model. Compounds 9-12 have potential anti-inflammatory activity and compound 9 can serve as lead compound for further development. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.08.020

文献信息

• Indole-3-ethylsulfamoylphenylacrylamides: Potent histone deacetylase inhibitors with anti-inflammatory activity
  作者：Samir Mehndiratta、Yi-Ling Hsieh、Yi-Min Liu、Amber Weiching Wang、Hsueh-Yun Lee、Lung-Yu Liang、Sunil Kumar、Che-Ming Teng、Chia-Ron Yang、Jing-Ping Liou

  DOI：10.1016/j.ejmech.2014.08.020

  日期：2014.10

  A series of 2-methyl-1H-indol-3-ethylsulfamoylphenylacrylamides based on LBH589-PXD101 core have been synthesized and evaluated for their histone deacetylase (HDAC) inhibitory and anti-inflammatory activity. In vitro, compounds 9-12 show 2.6-fold better HDAC inhibition and 3-fold better IL-6 suppression compared to LBH589.HCl (1.HCl). Furthermore, these compounds did not show apparent cell viability suppression on macrophages while in contrast, treatment with 1.HCl resulted in significant reduction in cell viability as demonstrated by an MTT assay. Repressed expression of iNOS, COX-2 and reduced phosphorylation of p65 revealed the inhibitory effect of these analogues on inflammatory mediator release which is related to inhibited NF-kappa B signals. (N-Hydroxy-3-3-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide) (9), exhibited ability superior to that of 1.HCl, was able to reduce carrageenan-induced acute inflammation in an animal model. Compounds 9-12 have potential anti-inflammatory activity and compound 9 can serve as lead compound for further development. (C) 2014 Elsevier Masson SAS. All rights reserved.