5-[2-(Ethoxycarbonyl)ethyl]-2-methoxybenzoic acid | 334014-89-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-[2-(Ethoxycarbonyl)ethyl]-2-methoxybenzoic acid
• 英文别名: 5-(3-Ethoxy-3-oxopropyl)-2-methoxybenzoic acid
• CAS: 334014-89-0
• 化学式: C₁₃H₁₆O₅
• 分子量: 252.267
• InChiKey: ZBZXXKVWAZSUIR-UHFFFAOYSA-N

物化性质

• 沸点：
  393.5±32.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[2-(Ethoxycarbonyl)ethyl]-2-methoxybenzoic acid 在 sodium hydroxide 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.17h， 生成 3-[4-Methoxy-3-({[4-(trifluoromethyl)benzyl]amino}carbonyl)phenyl]propanoicacid
  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：

  5-((E)-2-Ethoxycarbonyl-vinyl)-2-methoxy-benzoic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 5-[2-(Ethoxycarbonyl)ethyl]-2-methoxybenzoic acid
  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

• CARBOXYLIC ACID DERIVATIVES AND DRUGS CONTAINING THE SAME
  申请人：Eisai Co., Ltd.

  公开号：EP1216980A1

  公开（公告）日：2002-06-26

  The present invention provides a novel carboxylic acid compound, a salt thereof or a hydrate of them useful as an insulin-resistant improver, and a medicament comprising the compound as an active ingredient. That is, the present invention provides a carboxylic acid compound represented by the following formula (I), a salt thereof, an ester thereof or a hydrate of them. In the formula, R1 represents hydrogen atom, hydroxyl group or a C1-6 alkyl group etc. which may have one or more substituents; L represents a single or double bond or a C1-6 alkylene group etc. which may have one or more substituents; M represents a single bond or a C1-6 alkylene group etc. which may have one or more substituents; T represents a single bond or a C1-3 alkylene group which may have one or more substituents; W represents carboxyl group or a group represented by the formula -CON(Rw1)Rw2 (wherein Rw1 and Rw2 are the same as or different from each other and each represents hydrogen atom, formyl group etc.) etc.; represents a single or double bond; X represents oxygen atom or a C2-6 alkenylene group etc. which may have one or more substituents; Y represents a C5-12 aromatic hydrocarbon group etc. which may have one or more substituents and which may have one or more heteroatoms; and ring Z represents a C5-6 aromatic hydrocarbon group which may have 0 to 4 substituents and which may have one or more heteroatoms.

  本发明提供了一种新型羧酸化合物、其盐或它们的水合物，可用作胰岛素抗性改进剂，以及包含该化合物作为活性成分的药物。也就是说，本发明提供了由下式（I）代表的羧酸化合物、其盐、酯或它们的水合物。 式中，R1 代表氢原子、羟基或 C1-6 烷基等，可有一个或多个取代基；L 代表单键或双键或 C1-6 亚烷基等，可有一个或多个取代基；M 代表单键或 C1-6 亚烷基等，可有一个或多个取代基。W 代表羧基或由式-CON(Rw1)Rw2 所代表的基团（其中 Rw1 和 Rw2 彼此相同或不同，且各自代表氢原子、甲酰基等）等。)等表示的基团；代表单键或双键；X 代表氧原子或 C2-6 烯基等，可有一个或多个取代基；Y 代表 C5-12 芳烃基等，可有一个或多个取代基，可有一个或多个杂原子；环 Z 代表 C5-6 芳烃基，可有 0 至 4 个取代基，可有一个或多个杂原子。
• Design, synthesis, and evaluation of a novel series of α-substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor (PPAR) α/δ dual agonists for the treatment of metabolic syndrome
  作者：Jun-ichi Kasuga、Daisuke Yamasaki、Yoko Araya、Aya Nakagawa、Makoto Makishima、Takefumi Doi、Yuichi Hashimoto、Hiroyuki Miyachi

  DOI：10.1016/j.bmc.2006.09.001

  日期：2006.12

  A series of alpha-alkyl-substituted phenylpropanoic acids was prepared as dual agonists of peroxisome proliferator-activated receptors alpha and delta (PPAR alpha/delta). Structure-activity relationship studies indicated that the shape of the linking group and the shape of the substituent at the distal benzene ring play key roles in determining the potency and the selectivity of PPAR subtype transactivation. Structure-activity relationships among the amide series (10) and the reversed amide series (13) are similar, but not identical, especially in the case of the compounds bearing a bulky hydrophobic substituent at the distal benzene ring, indicating that the hydrophobic tail part of the molecules in these two series binds at somewhat different positions in the large binding pocket of PPAR. alpha-Alkyl-substituted phenylpropanoic acids of (S)-configuration were identified as potent human PPAR alpha/delta dual agonists. Representative compounds exhibited marked nuclear receptor selectivity for PPAR alpha and PPAR delta. Subtype-selective PPAR activation was also examined by analysis of the mRNA expression of PPAR-regulated genes. (c) 2006 Elsevier Ltd. All rights reserved.
• Design, synthesis and evaluation of substituted phenylpropanoic acid derivatives as peroxisome proliferator-activated receptor (PPAR) activators: novel human PPARα-selective activators
  作者：Hiroyuki Miyachi、Masahiro Nomura、Takahiro Tanase、Yukie Takahashi、Tomohiro Ide、Masaki Tsunoda、Koji Murakami、Katsuya Awano

  DOI：10.1016/s0960-894x(01)00672-2

  日期：2002.1

  A series of substituted phenylpropanoic acid derivatives was prepared as part of a search for subtype-selective human peroxisome proliferator-activated receptor (PPAR) activators. Structure-activity relationship studies indicated that the substituent at the alpha -position of the carboxyl group plays a key role in determining the potency and the selectivity for PPAR trans activation. (C) 2001 Elsevier Science Ltd. All rights reserved.
• US6884821B1
  申请人：——

  公开号：US6884821B1

  公开（公告）日：2005-04-26
• 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，