(S,E)-methyl 7-(3-(4-(4-bromobenzyloxy)phenyl)acrylamido)-8-oxo-8-(quinolin-8-ylamino)octanoate | 1260378-05-9

• 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: (S,E)-methyl 7-(3-(4-(4-bromobenzyloxy)phenyl)acrylamido)-8-oxo-8-(quinolin-8-ylamino)octanoate
• CAS: 1260378-05-9
• 化学式: C₃₄H₃₄BrN₃O₅
• 分子量: 644.565
• InChiKey: UASQNYLRKRTAAC-UKWOOVPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.84
• 重原子数：
  43.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  106.62
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S,E)-methyl 7-(3-(4-(4-bromobenzyloxy)phenyl)acrylamido)-8-oxo-8-(quinolin-8-ylamino)octanoate 在 盐酸羟胺 、 potassium tert-butylate 作用下， 以 甲醇 为溶剂， 以13%的产率得到(S,E)-2-(3-(4-(4-bromobenzyloxy)phenyl)acrylamido)-N(8)-hydroxy-N(1)-(quinolin-8-yl)octanediamide
  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：

  (E)‐3‐(4‐((4‐bromobenzyl)oxy)phenyl)acrylic acid 、 (S)-methyl 7-amino-8-oxo-8-(quinolin-8-ylamino)octanoate trifluoroacetate 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 、 苯 为溶剂， 反应 48.0h， 以82%的产率得到(S,E)-methyl 7-(3-(4-(4-bromobenzyloxy)phenyl)acrylamido)-8-oxo-8-(quinolin-8-ylamino)octanoate
  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