ethyl 2-ethyl-3-[3-[4-(trifluoromethyl)benzoylaminomethyl]-4-methoxyphenyl]propanoate | 334015-34-8

• 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: ethyl 2-ethyl-3-[3-[4-(trifluoromethyl)benzoylaminomethyl]-4-methoxyphenyl]propanoate
• 英文别名: ethyl 2-[4-methoxy-3-({[4-(trifluoromethyl)benzoyl]amino}methyl)benzyl]butanoate；ethyl 2-[[4-methoxy-3-[[[4-(trifluoromethyl)benzoyl]amino]methyl]phenyl]methyl]butanoate
• CAS: 334015-34-8
• 化学式: C₂₃H₂₆F₃NO₄
• 分子量: 437.459
• InChiKey: OCBMRLANLQWLAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-ethyl-3-[3-[4-(trifluoromethyl)benzoylaminomethyl]-4-methoxyphenyl]propanoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 2-[4-methoxy-3-({[4-(trifluoromethyl)benzoyl]amino}methyl]benzyl]butanoic 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
• 作为产物：
  描述：

  4-三氟甲基苯甲酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 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

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α（PPARα）的配体结合，激活并表现出强效的降脂作用，并提供了制备它们的方法。它涉及由通式（1）1表示的取代苯丙酸衍生物，其中R1表示具有1至4个碳原子的较低烷基基团，具有1至3个碳原子的较低烷氧基团，三氟甲基基团，三氟甲氧基团，苯基（未取代或可能具有取代基团），苯氧基（未取代或可能具有取代基团）或苄氧基（未取代或可能具有取代基团），R2表示氢原子，具有1至4个碳原子的较低烷基基团或具有1至3个碳原子的较低烷氧基团，R3表示具有1至3个碳原子的较低烷氧基团，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，以及制备它们的方法。
• Carboxylic acid derivatives and drugs containing the same
  申请人：Shinoda Masanobu

  公开号：US06884821B1

  公开（公告）日：2005-04-26

  Novel carboxylic acid derivatives of general formula (I), salts of the same, esters thereof, or hydrates of them, which are useful as insulin resistance improvers; and drugs containing the derivatives as the active ingredient. In said formula, R 1 is hydrogen, hydroxyl, alkyl, or the like; L is a single bond, a double bond, alkylene, or the like; M is a single bond, alkylene, or the like; T is a single bond, alkylene, or the like; W is carboxyl, —CON(R W1 )R W2 , or the like; represents a single or double bond; X is oxygen, alkenylene, or the like; Y is an aromatic hydrocarbon group which may contain a heteroatom, or the like; and Z is an aromatic hydrocarbon group which may contain a heteroatom.

  化合物的一般式（I）的新型羧酸衍生物，其盐、酯或水合物，可用作胰岛素抵抗改善剂；以及含有该衍生物作为活性成分的药物。在所述的公式中，R1是氢、羟基、烷基或类似物；L是单键、双键、烷基或类似物；M是单键、烷基或类似物；T是单键、烷基或类似物；W是羧基、—CON（RW1）RW2或类似物；表示单键或双键；X是氧、烯基烷基或类似物；Y是芳香族碳氢基团，可以包含杂原子或类似物；Z是芳香族碳氢基团，可以包含杂原子。
• 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。
• SUBSTITUTED PHENYLPROPIONIC ACID DERIVATIVES
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP1285908A1

  公开（公告）日：2003-02-26

  The invention provides novel substituted phenylpropionic acid derivatives that bind to the receptor as ligands of human peroxisome proliferator-activated receptor α (PPARα) 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) [wherein R1 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, R2 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, R3 denotes a lower alkoxy group with carbon atoms of 1 to 3, and the binding mode of A portion denotes -CH2CONH-, -NHCOCH2-, -CH2CH2CO-, -CH2CH2CH2-, -CH2CH2O-, -CONHCH2-, -CH2NHCH2-, -COCH2O-, -OCH2CO-, -COCH2NH- or -NHCH2CO-], their pharmaceutically acceptable salts and their hydrates, and processes for preparing them.

  本发明提供了新型取代的苯基丙酸衍生物，这些衍生物作为人类过氧化物酶体增殖激活受体α（PPARα）的配体与受体结合，从而激活并表现出强效的降脂作用，本发明还提供了制备这些衍生物的工艺。 它涉及通式（1）所代表的取代苯丙酸衍生物 [其中 R1 表示碳原子数为 1 至 4 的低级烷基、碳原子数为 1 至 3 的低级烷氧基、三氟甲基、三氟甲氧基、未取代或可能有取代基的苯基、未取代或可能有取代基的苯氧基或未取代或可能有取代基的苄氧基，R2 表示氢原子、R2表示氢原子、碳原子数为 1 至 4 的低级烷基或碳原子数为 1 至 3 的低级烷氧基，R3 表示碳原子数为 1 至 3 的低级烷氧基，A 部分的结合方式表示-CH2CONH-、-NHCOCH2-、-CH2CH2CO-、-CH2CH2CH2-、-CH2CH2O-、-CONHCH2-、-CH2NHCH2-、-COCH2O-、-OCH2CO-、-COCH2NH-或-NHCH2CO-]，它们的药学上可接受的盐和它们的水合物，以及制备它们的工艺。
• 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.