octanedioic acid {2'-[2-amino-3-(1H-indol-3-yl)-propionylamino]biphenyl-4-yl}amide hydroxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: octanedioic acid {2'-[2-amino-3-(1H-indol-3-yl)-propionylamino]biphenyl-4-yl}amide hydroxamide
• 英文别名: octanedioic acid {2'-[2-amino-3-(1H-indol-3-yl)-propionylamino]-biphenyl-4-yl}-amide hydroxyamide；N-[4-[2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]phenyl]phenyl]-N'-hydroxyoctanediamide
• 化学式: C₃₁H₃₅N₅O₄
• 分子量: 541.65
• InChiKey: ACGVFMBQNSCSQI-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  149
• 氢给体数：
  6
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-L-色氨酸 在 palladium dihydroxide 、 palladium on activated charcoal 吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 octanedioic acid {2'-[2-amino-3-(1H-indol-3-yl)-propionylamino]biphenyl-4-yl}amide hydroxamide
  参考文献：
  名称：

  Functional Differences in Epigenetic ModulatorsSuperiority of Mercaptoacetamide-Based Histone Deacetylase Inhibitors Relative to Hydroxamates in Cortical Neuron Neuroprotection Studies

  摘要：

  We compare the ability of two structurally different classes of epigenetic modulators, namely, histone deacetylase (HDAC) inhibitors containing either a hydroxamate or a mercaptoacetamide as the zinc binding group, to protect cortical neurons in culture from oxidative stress-induced death. This study reveals that some of the mercaptoacetamide-based HDAC inhibitors are fully protective, whereas the hydroxamates show toxicity at higher concentrations. Our present results appear to be consistent with the possibility that the mercaptoacetamide-based HDAC inhibitors interact with a different subset of the HDAC isozymes [less activity at HDAC1 and 2 correlates with less inhibitor toxicity], or alternatively, are interacting selectively with only the cytoplasmic HDACs that are crucial for protection from oxidative stress.

  DOI：

  10.1021/jm070178x

文献信息

• WO2008/19025
  申请人：——

  公开号：——

  公开（公告）日：——
• Functional Differences in Epigenetic ModulatorsSuperiority of Mercaptoacetamide-Based Histone Deacetylase Inhibitors Relative to Hydroxamates in Cortical Neuron Neuroprotection Studies
  作者：Alan P. Kozikowski、Yufeng Chen、Arsen Gaysin、Bin Chen、Melissa A. D'Annibale、Carla M. Suto、Brett C. Langley

  DOI：10.1021/jm070178x

  日期：2007.6.1

  We compare the ability of two structurally different classes of epigenetic modulators, namely, histone deacetylase (HDAC) inhibitors containing either a hydroxamate or a mercaptoacetamide as the zinc binding group, to protect cortical neurons in culture from oxidative stress-induced death. This study reveals that some of the mercaptoacetamide-based HDAC inhibitors are fully protective, whereas the hydroxamates show toxicity at higher concentrations. Our present results appear to be consistent with the possibility that the mercaptoacetamide-based HDAC inhibitors interact with a different subset of the HDAC isozymes [less activity at HDAC1 and 2 correlates with less inhibitor toxicity], or alternatively, are interacting selectively with only the cytoplasmic HDACs that are crucial for protection from oxidative stress.