(E)-ethyl 3-{5-{{[2-(benzo[d][1,3]dioxol-5-yl)ethyl](2-phenoxybutyl)amino}methyl}furan-2-yl}acrylate | 1450591-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (E)-ethyl 3-{5-{{[2-(benzo[d][1,3]dioxol-5-yl)ethyl](2-phenoxybutyl)amino}methyl}furan-2-yl}acrylate
• CAS: 1450591-23-7
• 化学式: C₂₉H₃₃NO₆
• 分子量: 491.584
• InChiKey: ZGVOCAMTCXVHKV-FYWRMAATSA-N

物化性质

• 沸点：
  615.8±55.0 °C(predicted)
• 密度：
  1.191±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.49
• 重原子数：
  36.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  70.37
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (E)-ethyl 3-{5-{{[2-(benzo[d][1,3]dioxol-5-yl)ethyl](2-phenoxybutyl)amino}methyl}furan-2-yl}acrylate 在 羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以37.2%的产率得到(E)-3-{5-{{[2-(benzo[d][1,3]dioxol-5-yl)ethyl](4-phenoxybutyl)amino}methyl}furan-2-yl}-N-hydroxyacrylamide
  参考文献：
  名称：

  Novel N-hydroxyfurylacrylamide-based histone deacetylase (HDAC) inhibitors with branched CAP group (Part 2)

  摘要：

  Histone deacetylases (HDACs) are significant enzymes involved in tumor genesis and development. Herein, we report a series of novel N-hydroxyfurylacryl-amide-based HDAC inhibitors, which are marked by introducing branched hydrophobic groups as the capping group. The inhibitory activity of the synthesized compounds against HDACs and several tumor cell lines are firstly determined. Fifteen compounds with promising activities are selected for further evaluation of target selectivity profile against recombinant human HDAC1, HDAC4 and HDAC6. Compounds 10a, 10b, 10d and 16a exhibit outstanding selectivity against HDAC6. Analysis of HDAC4 X-ray structure and HDAC1, HDAC6 homology model indicates that these enzyme differ significantly in the rim near the surface of the active site. Although TSA has been known as a pan-HDAC inhibitor, it exhibits outstanding selectivity for HDAC6 over HDAC4. For further physicochemical properties study, six compounds are chosen for determination of their physicochemical properties including logD(7.4) and aqueous solubility. The results suggest that compounds with a smaller framework and with hydrophilicgroups are likely to have better aqueous solubility. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.009
• 作为产物：
  描述：

  2-膦酰丁酸三乙脂 在 sodium tetrahydroborate 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 potassium iodide 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 15.83h， 生成 (E)-ethyl 3-{5-{{[2-(benzo[d][1,3]dioxol-5-yl)ethyl](2-phenoxybutyl)amino}methyl}furan-2-yl}acrylate
  参考文献：
  名称：

  Novel N-hydroxyfurylacrylamide-based histone deacetylase (HDAC) inhibitors with branched CAP group (Part 2)

  摘要：

  Histone deacetylases (HDACs) are significant enzymes involved in tumor genesis and development. Herein, we report a series of novel N-hydroxyfurylacryl-amide-based HDAC inhibitors, which are marked by introducing branched hydrophobic groups as the capping group. The inhibitory activity of the synthesized compounds against HDACs and several tumor cell lines are firstly determined. Fifteen compounds with promising activities are selected for further evaluation of target selectivity profile against recombinant human HDAC1, HDAC4 and HDAC6. Compounds 10a, 10b, 10d and 16a exhibit outstanding selectivity against HDAC6. Analysis of HDAC4 X-ray structure and HDAC1, HDAC6 homology model indicates that these enzyme differ significantly in the rim near the surface of the active site. Although TSA has been known as a pan-HDAC inhibitor, it exhibits outstanding selectivity for HDAC6 over HDAC4. For further physicochemical properties study, six compounds are chosen for determination of their physicochemical properties including logD(7.4) and aqueous solubility. The results suggest that compounds with a smaller framework and with hydrophilicgroups are likely to have better aqueous solubility. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.009