(E)-N-hydroxy-2-[(naphthalen-2-yl)methoxy]-4-methoxycinnamamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-N-hydroxy-2-[(naphthalen-2-yl)methoxy]-4-methoxycinnamamide
• 英文别名: (E)-N-hydroxy-3-[4-methoxy-2-(naphthalen-2-ylmethoxy)phenyl]prop-2-enamide
• 化学式: C₂₁H₁₉NO₄
• 分子量: 349.386
• InChiKey: KJNGAEYGXRBHML-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-甲氧基香豆素 在 盐酸羟胺 、 potassium carbonate 、 三乙胺 、 potassium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 34.0h， 生成 (E)-N-hydroxy-2-[(naphthalen-2-yl)methoxy]-4-methoxycinnamamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation ofortho-ArylN-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors

  摘要：

  AbstractHistone deacetylases (HDACs) are a family of enzymes that play a crucial role in biological process and diseases. In contrast to other isozymes, HDAC8 is uniquely incapable of histone acetylation. In order to delineate its physiological function, we developed HDAC8‐selective inhibitors using knowledge‐based design combined with structural modeling techniques. Enzyme inhibitory analysis demonstrated that some of the resulting compounds (22 b, 22 d, 22 f, and 22 g) exhibited anti‐HDAC8 activity superior to PCI34051, a known HDAC8‐specific inhibitor, with IC50 values in the range of 5–50 nM. Among them, compound 22 d showed antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1‐5); it exhibited cytotoxicity against human lung CL1‐5 cells similar to that of SAHA yet without significant cytotoxicity for normal IMR‐90 cells. Expression profiling of HDAC isoforms in three cancer cell lines indicated that the HDAC8 level in CL1‐5 is higher than that in H1299 and CL1‐1 cells, a result consistent with the differential cytotoxicity of compound 22 d. These results suggest the effectiveness of our design concept, which may lead to a tool compound for studying the specific role of HDAC8 in cellular biological processes.

  DOI：

  10.1002/cmdc.201200300

文献信息

• Synthesis and Biological Evaluation of<i>ortho</i>-Aryl<i>N</i>-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors
  作者：Wei-Jan Huang、Yi-Ching Wang、Shi-Wei Chao、Chen-Yui Yang、Liang-Chieh Chen、Mei-Hsiang Lin、Wen-Chi Hou、Mei-Yu Chen、Tai-Lin Lee、Ping Yang、Chung-I Chang

  DOI：10.1002/cmdc.201200300

  日期：2012.10

  AbstractHistone deacetylases (HDACs) are a family of enzymes that play a crucial role in biological process and diseases. In contrast to other isozymes, HDAC8 is uniquely incapable of histone acetylation. In order to delineate its physiological function, we developed HDAC8‐selective inhibitors using knowledge‐based design combined with structural modeling techniques. Enzyme inhibitory analysis demonstrated that some of the resulting compounds (22 b, 22 d, 22 f, and 22 g) exhibited anti‐HDAC8 activity superior to PCI34051, a known HDAC8‐specific inhibitor, with IC50 values in the range of 5–50 nM. Among them, compound 22 d showed antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1‐5); it exhibited cytotoxicity against human lung CL1‐5 cells similar to that of SAHA yet without significant cytotoxicity for normal IMR‐90 cells. Expression profiling of HDAC isoforms in three cancer cell lines indicated that the HDAC8 level in CL1‐5 is higher than that in H1299 and CL1‐1 cells, a result consistent with the differential cytotoxicity of compound 22 d. These results suggest the effectiveness of our design concept, which may lead to a tool compound for studying the specific role of HDAC8 in cellular biological processes.