5-(3-Ethoxy-2-methyl-3-oxopropyl)-2-methoxybenzoic acid | 311770-44-2

• 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-(3-Ethoxy-2-methyl-3-oxopropyl)-2-methoxybenzoic acid
• CAS: 311770-44-2
• 化学式: C₁₄H₁₈O₅
• 分子量: 266.294
• InChiKey: UECMXJXNMVOTJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 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-(3-Ethoxy-2-methyl-3-oxopropyl)-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-benzylcarbamoyl)-phenyl]-2-methyl-propionic 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：

  benzyl 5-formyl-2-methoxybenzoate 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 20.0 ℃ 、353.0 kPa 条件下， 反应 8.5h， 生成 5-(3-Ethoxy-2-methyl-3-oxopropyl)-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

• 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.
• SUBSTITUTED PHENYLPROPIONIC ACID DERIVATIVES AS AGONISTS TO HUMAN PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA(PPAR)
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP1184366B1

  公开（公告）日：2005-02-09
• 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，