ethyl (E)-3-(2-methoxy-4-phenylmethoxyphenyl)prop-2-enoate | 1417997-45-5

• 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: ethyl (E)-3-(2-methoxy-4-phenylmethoxyphenyl)prop-2-enoate
• CAS: 1417997-45-5
• 化学式: C₁₉H₂₀O₄
• 分子量: 312.365
• InChiKey: KRXFFAKIGUTZKX-ZRDIBKRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (E)-3-(2-methoxy-4-phenylmethoxyphenyl)prop-2-enoate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 (E)-3-(2-methoxy-4-phenylmethoxyphenyl)prop-2-enoic acid
  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
• 作为产物：
  描述：

  7-羟基香豆素 在 potassium carbonate 作用下， 反应 30.0h， 生成 ethyl (E)-3-(2-methoxy-4-phenylmethoxyphenyl)prop-2-enoate
  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

• Phenyl derivatives, their manufacture and use as pharmaceutical agents
  申请人：Ackermann Jean

  公开号：US20050096337A1

  公开（公告）日：2005-05-05

  This invention relates to compounds of the formula wherein one of R 5 , R 6 and R 7 is and X 1 , X 2 , Y 1 to Y 4 , R 1 to R 13 and m and n are defined in the description, and to all enantiomers and pharmaceutically acceptable salts and/or esters thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by PPARδ and/or PPARα agonists.

  这项发明涉及以下结构的化合物 其中R 5 、R 6 和R 7 中的一个是 以及X 1 、X 2 、Y 1 到Y 4 、R 1 到R 13 以及m和n在描述中有定义，以及所有的对映体和药用上可接受的盐和/或酯。该发明还涉及含有这类化合物的药物组合物，以及用于制备它们的方法以及它们用于治疗和/或预防由PPARδ和/或PPARα激动剂调节的疾病的用途。
• Phenyl derivatives as PPAR agonists
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2314576A1

  公开（公告）日：2011-04-27

  This invention relates to compounds of the formula wherein one of R5, R6 and R7 is and X1, X2, Y1 to Y4, R1 to R13 and m and n are as defined in the description, and to all enantiomers and pharmaceutically acceptable salts and/or esters thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by PPARδ and/or PPARα agonists.

  本发明涉及式如下的化合物 其中 R5、R6 和 R7 之一为 和 X1、X2、Y1 至 Y4、R1 至 R13 以及 m 和 n 如描述中所定义的化合物，以及它们的所有对映体和药学上可接受的盐和/或酯。本发明还涉及含有此类化合物的药物组合物、其制备工艺以及其用于治疗和/或预防受 PPARδ 和/或 PPARα 激动剂调节的疾病的用途。
• HDAC8 inhibitors for treating cancer
  申请人：City of Hope

  公开号：US10308596B2

  公开（公告）日：2019-06-04

  Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.

  本文特别提供了通过抑制 HDAC8 治疗癌症的化合物和方法。
• PHENYL DERIVATIVES AS PPAR AGONISTS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1682508A1

  公开（公告）日：2006-07-26
• HDAC8 INHIBITORS FOR TREATING CANCER
  申请人：City of Hope

  公开号：US20170050922A2

  公开（公告）日：2017-02-23

  Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.