ethyl 2-ethyl-3-(4-methoxyphenyl)acrylate | 53618-36-3

• 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 2-ethyl-3-(4-methoxyphenyl)acrylate
• 英文别名: ethyl 2-(4-methoxybenzylidene)butanoate；p-Methoxy-α-aethylzimtsaeureaethylester；ethyl 2-[(4-methoxyphenyl)methylidene]butanoate
• CAS: 53618-36-3
• 化学式: C₁₄H₁₈O₃
• 分子量: 234.295
• InChiKey: FDWYHUUQGAURAS-UHFFFAOYSA-N

物化性质

• 沸点：
  348.2±17.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-ethyl-3-(4-methoxyphenyl)acrylate 在 palladium on activated charcoal 吡啶 、 盐酸羟胺 、 氢气 、 四氯化钛 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， -20.0~20.0 ℃ 、294.3 kPa 条件下， 反应 12.0h， 生成 ethyl 2-ethyl-3-[3-[4-(trifluoromethyl)benzoylaminomethyl]-4-methoxyphenyl]propanoate
  参考文献：
  名称：

  设计，合成和评估取代的苯基丙酸衍生物作为人过氧化物酶体增殖物激活的受体激活剂。发现有效的人过氧化物酶体增殖物激活受体α亚型选择性激活剂。

  摘要：

  制备取代的苯基丙酸衍生物，作为寻找亚型选择性人过氧化物酶体增殖物激活受体α（PPARalpha）激活剂的一部分。构效关系研究表明，取代基在含有羧基的头部的α位，羧基与中心苯环之间的距离，中心苯环与苯环之间的连接基团的位置和立体化学特征。远端苯环和分子远端疏水尾部的取代基在确定PPAR亚型反式激活的效力和选择性中都起着关键作用。这项研究已导致鉴定出有效和人源的PPARalpha选择性旋光性α-烷基苯基丙酸衍生物，

  DOI：

  10.1021/jm0205144
• 作为产物：
  描述：

  2-膦酰丁酸三乙脂 、 4-甲氧基苯甲醛 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 ethyl 2-ethyl-3-(4-methoxyphenyl)acrylate
  参考文献：
  名称：

  设计，合成和评估取代的苯基丙酸衍生物作为人过氧化物酶体增殖物激活的受体激活剂。发现有效的人过氧化物酶体增殖物激活受体α亚型选择性激活剂。

  摘要：

  制备取代的苯基丙酸衍生物，作为寻找亚型选择性人过氧化物酶体增殖物激活受体α（PPARalpha）激活剂的一部分。构效关系研究表明，取代基在含有羧基的头部的α位，羧基与中心苯环之间的距离，中心苯环与苯环之间的连接基团的位置和立体化学特征。远端苯环和分子远端疏水尾部的取代基在确定PPAR亚型反式激活的效力和选择性中都起着关键作用。这项研究已导致鉴定出有效和人源的PPARalpha选择性旋光性α-烷基苯基丙酸衍生物，

  DOI：

  10.1021/jm0205144

文献信息

• Substituted phenylpropionic acid derivatives
  申请人：——

  公开号：US20030187068A1

  公开（公告）日：2003-10-02

  The invention provides novel substituted phenylpropionic acid derivatives that bind to the receptor as ligands of human peroxisome proliferator-activated receptor a (PPAR&agr;) to activate and exhibit potent lipid-decreasing action, and processes for preparing them. It relates to substituted phenylpropionic acid derivatives represented by a general formula (1) 1 [wherein R 1 denotes a lower alkyl group with carbon atoms of 1 to 4, lower alkoxy group with carbon atoms of 1 to 3, trifluoromethyl group, trifluoromethoxy group, phenyl group which is unsubstituted or may have substituents, phenoxy group which is unsubstituted or may have substituents or benzyloxy group which is unsubstituted or may have substituents, R 2 denotes a hydrogen atom, lower alkyl group with carbon atoms of 1 to 4 or lower alkoxy group with carbon atoms of 1 to 3, R 3 denotes a lower alkoxy group with carbon atoms of 1 to 3, and the binding mode of A portion denotes —CH 2 CONH—, —NHCOCH 2 —, —CH 2 CH 2 CO—, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 O—, —CONHCH 2 —, —CH2NHCH 2 —, —COCH 2 O—, —OCH 2 CO—, —COCH 2 NH— or —CHCH 2 CO—], their pharmaceutically acceptable salts and their hydrates, and processes for preparing them.

  该发明提供了新型取代苯丙酸衍生物，它们作为人类过氧化物酶体增殖物激活受体a (PPAR&agr;)的配体结合到受体上，激活并表现出强效的降脂作用，并提供了其制备方法。它涉及到由通式(1)1[表示的取代苯丙酸衍生物，其中R1表示具有1到4个碳原子的低级烷基，具有1到3个碳原子的低级烷氧基，三氟甲基基团，三氟甲氧基基团，未取代或可能具有取代基团的苯基，未取代或可能具有取代基团的苯氧基或未取代或可能具有取代基团的苄氧基，R2表示氢原子，具有1到4个碳原子的低级烷基或具有1到3个碳原子的低级烷氧基，R3表示具有1到3个碳原子的低级烷氧基，A部分的结合模式表示为—CH2CONH—、—NHCOCH2—、—CH2CH2CO—、—CH2CH2CH2—、—CH2CH2O—、—CONHCH2—、—CH2NHCH2—、—COCH2O—、—OCH2CO—、—COCH2NH—或—CHCH2CO—]，它们的药学上可接受的盐和水合物，以及它们的制备方法。
• Design, synthesis, and evaluation of potent, structurally novel peroxisome proliferator-activated receptor (PPAR) δ-selective agonists
  作者：Jun-ichi Kasuga、Izumi Nakagome、Atsushi Aoyama、Kumiko Sako、Michiyasu Ishizawa、Michitaka Ogura、Makoto Makishima、Shuichi Hirono、Yuichi Hashimoto、Hiroyuki Miyachi

  DOI：10.1016/j.bmc.2007.05.023

  日期：2007.8

  A series of 3-(4-alkoxyphenyl)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) 6-selective agonists, based on our previously discovered potent human PPAR alpha/delta dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPAR delta transactivation activity and highest PPAR delta selectivity. The (S)-enantiomer of a representative compound exhibited extremely potent PPAR delta transactivation activity, comparable with or somewhat superior to that of the known PPAR delta-selective agonist, GW-501516. The representative compound regulated the expression of genes involved in lipid and glucose homeostasis, and should be useful not only as a chemical tool to study PPAR delta function, but also as a candidate drug for the treatment of metabolic syndrome. (c) 2007 Elsevier Ltd. All rights reserved.
• Improvement of the transactivation activity of phenylpropanoic acid-type peroxisome proliferator-activated receptor pan agonists: Effect of introduction of fluorine at the linker part
  作者：Jun-ichi Kasuga、Takuji Oyama、Yuko Hirakawa、Makoto Makishima、Kosuke Morikawa、Yuichi Hashimoto、Hiroyuki Miyachi

  DOI：10.1016/j.bmcl.2008.07.046

  日期：2008.8

  We developed a potent peroxisome proliferator-activated receptor pan agonist (a candidate drug for treatment of altered metabolic homeostasis) by introducing fluorine atoms at appropriate position(s) of the known phenylpropionic acid-type pan agonist TIPP-703. (c) 2008 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Evaluation of Substituted Phenylpropanoic Acid Derivatives as Human Peroxisome Proliferator Activated Receptor Activators. Discovery of Potent and Human Peroxisome Proliferator Activated Receptor α Subtype-Selective Activators
  作者：Masahiro Nomura、Takahiro Tanase、Tomohiro Ide、Masaki Tsunoda、Masahiro Suzuki、Hideharu Uchiki、Koji Murakami、Hiroyuki Miyachi

  DOI：10.1021/jm0205144

  日期：2003.8.1

  Substituted phenylpropanoic acid derivatives were prepared as part of a search for subtype-selective human peroxisome proliferator activated receptor alpha (PPARalpha) activators. Structure-activity relationship studies indicated that the nature and the stereochemistry of the substituent at the alpha-position of the head part containing the carboxyl group, the distance between the carboxyl group and

  制备取代的苯基丙酸衍生物，作为寻找亚型选择性人过氧化物酶体增殖物激活受体α（PPARalpha）激活剂的一部分。构效关系研究表明，取代基在含有羧基的头部的α位，羧基与中心苯环之间的距离，中心苯环与苯环之间的连接基团的位置和立体化学特征。远端苯环和分子远端疏水尾部的取代基在确定PPAR亚型反式激活的效力和选择性中都起着关键作用。这项研究已导致鉴定出有效和人源的PPARalpha选择性旋光性α-烷基苯基丙酸衍生物，
• Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator-activated receptor (PPAR) α-selective agonists
  作者：Shintaro Ban、Jun-ichi Kasuga、Izumi Nakagome、Hiromi Nobusada、Fusako Takayama、Shuichi Hirono、Hiromu Kawasaki、Yuichi Hashimoto、Hiroyuki Miyachi

  DOI：10.1016/j.bmc.2011.03.064

  日期：2011.5

  A series of alpha-ethylphenylpropanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) alpha-selective agonists, based on our PPAR alpha/delta dual agonist 3 as a lead compound. Structure-activity relationship studies clearly indicated that the steric bulkiness and position of the distal hydrophobic tail part are critical for PPAR alpha agonistic activity and PPAR alpha selectivity, as had been predicted from a molecular-modeling study. A representative compound blocked the progression of nonalcoholic steatohepatitis (NASH) in an animal model. (C) 2011 Elsevier Ltd. All rights reserved.