methyl (S)-4-(2-(2-chlorobenzamido)-3-(1H-indol-3-yl)propanamido)benzoate

• 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: methyl (S)-4-(2-(2-chlorobenzamido)-3-(1H-indol-3-yl)propanamido)benzoate
• 英文别名: methyl 4-[[(2S)-2-[(2-chlorobenzoyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]benzoate
• 化学式: C₂₆H₂₂ClN₃O₄
• 分子量: 475.931
• InChiKey: CFMYSPZFQVTMIS-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.59
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  100.29
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-4-(2-(2-chlorobenzamido)-3-(1H-indol-3-yl)propanamido)benzoate 在 羟胺钾盐 作用下， 以 甲醇 为溶剂， 以27%的产率得到(S)-2-chloro-N-(1-((4-(hydroxycarbamoyl)phenyl)amino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)benzamide
  参考文献：
  名称：

  Development of N-hydroxybenzamide derivatives with indole-containing cap group as histone deacetylases inhibitors

  摘要：

  Histone deacetylases inhibitors (HDACIs) have captured more and more attention in many diseases therapies, of which cancer is the most intractable. A novel series of N-hydroxybenzamide derivatives containing indole cap group was designed and synthesized. Most compounds exhibited excellent HDACs inhibitory activity, especially 8q-8v with low nanomolar IC50 values (1.5-13.0 nM), which were much more potent than the positive control SAHA. The most potent compound 8r showed slightly higher growth inhibitory activity than SAHA in multiple tumor cell lines, even though, antiproliferative activity of 8r seemed inferior to its HDAC inhibition activity. Poor transcellular permeability obtained from the result of HDAC class I cellular assay could explain the inferior antiproliferative activity. In addition, 8r displayed similar HDAC IIa cellular activity to class I, which indicated 8r might be a potent pan-HDAC inhibitor. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.040
• 作为产物：
  描述：

  4-氨基苯甲酸甲酯盐酸盐 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 5.0h， 生成 methyl (S)-4-(2-(2-chlorobenzamido)-3-(1H-indol-3-yl)propanamido)benzoate
  参考文献：
  名称：

  Development of N-hydroxybenzamide derivatives with indole-containing cap group as histone deacetylases inhibitors

  摘要：

  Histone deacetylases inhibitors (HDACIs) have captured more and more attention in many diseases therapies, of which cancer is the most intractable. A novel series of N-hydroxybenzamide derivatives containing indole cap group was designed and synthesized. Most compounds exhibited excellent HDACs inhibitory activity, especially 8q-8v with low nanomolar IC50 values (1.5-13.0 nM), which were much more potent than the positive control SAHA. The most potent compound 8r showed slightly higher growth inhibitory activity than SAHA in multiple tumor cell lines, even though, antiproliferative activity of 8r seemed inferior to its HDAC inhibition activity. Poor transcellular permeability obtained from the result of HDAC class I cellular assay could explain the inferior antiproliferative activity. In addition, 8r displayed similar HDAC IIa cellular activity to class I, which indicated 8r might be a potent pan-HDAC inhibitor. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.040

文献信息

• Development of N-hydroxybenzamide derivatives with indole-containing cap group as histone deacetylases inhibitors
  作者：Xiaoyang Li、Jingde Wu、Xiaoguang Li、Weiwei Mu、Xueliang Liu、Yiming Jin、Wenfang Xu、Yingjie Zhang

  DOI：10.1016/j.bmc.2015.08.040

  日期：2015.10

  Histone deacetylases inhibitors (HDACIs) have captured more and more attention in many diseases therapies, of which cancer is the most intractable. A novel series of N-hydroxybenzamide derivatives containing indole cap group was designed and synthesized. Most compounds exhibited excellent HDACs inhibitory activity, especially 8q-8v with low nanomolar IC50 values (1.5-13.0 nM), which were much more potent than the positive control SAHA. The most potent compound 8r showed slightly higher growth inhibitory activity than SAHA in multiple tumor cell lines, even though, antiproliferative activity of 8r seemed inferior to its HDAC inhibition activity. Poor transcellular permeability obtained from the result of HDAC class I cellular assay could explain the inferior antiproliferative activity. In addition, 8r displayed similar HDAC IIa cellular activity to class I, which indicated 8r might be a potent pan-HDAC inhibitor. (C) 2015 Elsevier Ltd. All rights reserved.