methyl (S)-7-(((benzyloxy)carbonyl)amino)-8-((3,4-dimethoxyphenethyl)amino)-8-oxooctanoate | 1286795-05-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (S)-7-(((benzyloxy)carbonyl)amino)-8-((3,4-dimethoxyphenethyl)amino)-8-oxooctanoate
• CAS: 1286795-05-8
• 化学式: C₂₇H₃₆N₂O₇
• 分子量: 500.592
• InChiKey: QALIOUZPCSEVOA-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 重原子数：
  36.0
• 可旋转键数：
  15.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  112.19
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-7-(((benzyloxy)carbonyl)amino)-8-((3,4-dimethoxyphenethyl)amino)-8-oxooctanoate 在 palladium 10% on activated carbon 、 三氟乙酸 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 以96%的产率得到methyl (S)-7-amino-8-((3,4-dimethoxyphenethyl)amino)-8-oxooctanoate
  参考文献：
  名称：

  Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components

  摘要：

  Malaria is the most lethal parasite-mediated tropical infectious disease, killing 1-2 million people each year. An emerging drug target is the enzyme Plasmodium falciparum histone deacetylase 1 (PfHDAC1). We report 26 compounds designed to bind the zinc and exterior surface around the entrance to the active site of PfHDAC1, 16 displaying potent in vitro antimalarial activity (IC(50) < 100 nM) against P. falciparum. Selected compounds were shown to cause hyperacetylation of P. falciparum histones and be > 10-fold more cytotoxic towards P. falciparum than a normal human cell type (NFF). Twenty-two inhibitors feature cinnamic acid derivatives or non-steroidal anti-inflammatory drugs (NSAIDs) as HDAC-binding components. A homology model of PfHDAC1 enzyme gives new insights to interactions likely made by some of these inhibitors. Results support PfHDAC1 as a promising new antimalarial drug target. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.096
• 作为产物：
  描述：

  Cbz-L-Asu(OMe)-OH 、 3,4-二甲氧基苯乙胺 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 48.0h， 以53%的产率得到methyl (S)-7-(((benzyloxy)carbonyl)amino)-8-((3,4-dimethoxyphenethyl)amino)-8-oxooctanoate
  参考文献：
  名称：

  Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components

  摘要：

  Malaria is the most lethal parasite-mediated tropical infectious disease, killing 1-2 million people each year. An emerging drug target is the enzyme Plasmodium falciparum histone deacetylase 1 (PfHDAC1). We report 26 compounds designed to bind the zinc and exterior surface around the entrance to the active site of PfHDAC1, 16 displaying potent in vitro antimalarial activity (IC(50) < 100 nM) against P. falciparum. Selected compounds were shown to cause hyperacetylation of P. falciparum histones and be > 10-fold more cytotoxic towards P. falciparum than a normal human cell type (NFF). Twenty-two inhibitors feature cinnamic acid derivatives or non-steroidal anti-inflammatory drugs (NSAIDs) as HDAC-binding components. A homology model of PfHDAC1 enzyme gives new insights to interactions likely made by some of these inhibitors. Results support PfHDAC1 as a promising new antimalarial drug target. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.096