N-hydroxy-3-{4-[2-(1H-indol-4-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-(1H-indol-4-yl)ethylsulfamoyl]phenyl}acrylamide
• 化学式: C₁₉H₁₉N₃O₄S
• 分子量: 385.444
• InChiKey: DFVAUEUMTWHQIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.21
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 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：

  4-(2-nitrovinyl)indole 在 吡啶 、 sodium tetrahydroborate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 铁粉 、 potassium carbonate 、 氯化铵 、 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 、 lithium hydroxide 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 29.25h， 生成 N-hydroxy-3-{4-[2-(1H-indol-4-yl)ethylsulfamoyl]phenyl}acrylamide
  参考文献：
  名称：

  4-Indolyl- N -hydroxyphenylacrylamides as potent HDAC class I and IIB inhibitors in vitro and in vivo

  摘要：

  A series of 4,5-indolyl-N-hydroxyphenylacrylamides, as HDAC inhibitors, has been synthesized and evaluated in vitro and in vivo. 4-Indolyl compounds 13 and 17 functions as potent inhibitors of HDAC1 (IC50 1.28 nM and 134 nM) and HDAC 2 (IC50 0.90 and 0.53 nM). N-Hydroxy-3-{4-[2-(1H-indo1-4-y1)-ethylsulfamoyl]-phenyl}-actylamide (13) inhibited the human cancer cell growth of PC3, A549, MDA-MB-231 and AsPC-1 with a GI(50) of 0.14, 0.25, 0.32, and 0.24 mu M, respectively. In in vivo evaluations bearing prostate PC3 xenografts nude mice model, compound 13 suppressed tumor growth with a tumor growth inhibition (TGI) of 62.2%. Immunohistochemistry of protein expressions, in PC-3 xenograft model indicated elevated acetyl-histone 3 and prominently inhibited HDAC2 protein expressions. Therefore, compound 13 could be a suitable lead for further investigation and the development of selective HDAC 2 inhibitors as potent anti-cancer compounds. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.079

文献信息

• 4-Indolyl- N -hydroxyphenylacrylamides as potent HDAC class I and IIB inhibitors in vitro and in vivo
  作者：Samir Mehndiratta、Ruei-Shian Wang、Han-Li Huang、Chih-Jou Su、Chia-Ming Hsu、Yi-Wen Wu、Shiow-Lin Pan、Jing-Ping Liou

  DOI：10.1016/j.ejmech.2017.03.079

  日期：2017.7

  A series of 4,5-indolyl-N-hydroxyphenylacrylamides, as HDAC inhibitors, has been synthesized and evaluated in vitro and in vivo. 4-Indolyl compounds 13 and 17 functions as potent inhibitors of HDAC1 (IC50 1.28 nM and 134 nM) and HDAC 2 (IC50 0.90 and 0.53 nM). N-Hydroxy-3-4-[2-(1H-indo1-4-y1)-ethylsulfamoyl]-phenyl}-actylamide (13) inhibited the human cancer cell growth of PC3, A549, MDA-MB-231 and AsPC-1 with a GI(50) of 0.14, 0.25, 0.32, and 0.24 mu M, respectively. In in vivo evaluations bearing prostate PC3 xenografts nude mice model, compound 13 suppressed tumor growth with a tumor growth inhibition (TGI) of 62.2%. Immunohistochemistry of protein expressions, in PC-3 xenograft model indicated elevated acetyl-histone 3 and prominently inhibited HDAC2 protein expressions. Therefore, compound 13 could be a suitable lead for further investigation and the development of selective HDAC 2 inhibitors as potent anti-cancer compounds. (C) 2017 Elsevier Masson SAS. All rights reserved.