ethyl 3-[3-(aminomethyl)-4-methoxyphenyl]-2-ethylpropanoate hydrochloride

• 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 3-[3-(aminomethyl)-4-methoxyphenyl]-2-ethylpropanoate hydrochloride
• 英文别名: ethyl 3-(3-aminomethyl-4-methoxyphenyl)-2-ethyl-propionate hydrochloride；ethyl 2-(3-(amino-methyl)-4-methoxybenzyl)butanoate hydrochloride；ethyl 2-[(3-aminomethyl-4-methoxyphenyl)-methyl]butyrate hydrochloride；ethyl 2-[[3-(aminomethyl)-4-methoxyphenyl]methyl]butanoate;hydrochloride
• 化学式: C₁₅H₂₃NO₃*ClH
• 分子量: 301.813
• InChiKey: VNPUWGKEOHHEIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.71
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-[3-(aminomethyl)-4-methoxyphenyl]-2-ethylpropanoate hydrochloride 在 三乙胺 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 2-(4-methoxy-3-((4-phenethoxybenzamido)methyl)benzyl)butanoic acid
  参考文献：
  名称：

  Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator-activated receptor (PPAR) α-selective agonists

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.03.064
• 作为产物：
  描述：

  2-膦酰丁酸三乙脂 在 吡啶 、 盐酸 、 palladium 10% on activated carbon 、 盐酸羟胺 、 氢气 、 四氯化钛 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 mineral oil 为溶剂， -20.0~50.0 ℃ 、353.01 kPa 条件下， 反应 19.0h， 生成 ethyl 3-[3-(aminomethyl)-4-methoxyphenyl]-2-ethylpropanoate hydrochloride
  参考文献：
  名称：

  Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator-activated receptor (PPAR) α-selective agonists

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.03.064

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。
• Substituted carboxylic acid derivatives
  申请人：Miyachi HIroyuki

  公开号：US20050101521A1

  公开（公告）日：2005-05-12

  The invention provides novel substituted carboxylic acid derivatives that bind to receptor as ligands of human peroxisome proliferator-activated receptor (PPAR) to activate it and exhibit potent triglyceride-lowering action, cholesterol-lowering action and blood glucose-lowering action, and processes for preparing them. The invention relates to substituted carboxylic acid derivatives represented by a general formula (1), their pharmaceutically acceptable salts and their hydrates, and processes for preparing them.

  本发明提供了一种新型的取代羧酸衍生物，它们作为人类过氧化物酶体增殖物激活受体（PPAR）的配体与受体结合，激活它并表现出强效的三酰甘油降低作用、降低胆固醇作用和降低血糖作用，并提供了其制备方法。本发明涉及一般式（1）所表示的取代羧酸衍生物及其药学上可接受的盐和水合物，以及它们的制备方法。
• 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。
• SUBSTITUTED CARBOXYLIC ACID DERIVATIVES
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP1348698A1

  公开（公告）日：2003-10-01

  The invention provides novel substituted carboxylic acid derivatives that bind to receptor as ligands of human peroxisome proliferator-activated receptor (PPAR) to activate it and exhibit potent triglyceride-lowering action, cholesterol-lowering action and blood glucose-lowering action, and processes for preparing them. The invention relates to substituted carboxylic acid derivatives represented by a general formula (1), their pharmaceutically acceptable salts and their hydrates, and processes for preparing them.

  本发明提供了新型取代的羧酸衍生物，这些衍生物作为人类过氧化物酶体增殖激活受体（PPAR）的配体与受体结合以激活受体，并表现出强效的降甘油三酯作用、降胆固醇作用和降血糖作用，还提供了制备这些衍生物的工艺。 本发明涉及通式（1）所代表的取代羧酸衍生物、 它们的药学上可接受的盐及其水合物，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.