ethyl 3-ethoxy-3-(4-((2-methylbenzyl)oxy)phenyl)propanoate | 1202576-94-0

• 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: ethyl 3-ethoxy-3-(4-((2-methylbenzyl)oxy)phenyl)propanoate
• 英文别名: ethyl 3-ethoxy-3{4-[(2-methylbenzyl)oxy]phenyl}propanoate；Ethyl 3-ethoxy-3-{4-[(2-methylbenzyl)oxy]phenyl}propionate；Ethyl 3-ethoxy-3-[4-[(2-methylphenyl)methoxy]phenyl]propanoate
• CAS: 1202576-94-0
• 化学式: C₂₁H₂₆O₄
• 分子量: 342.435
• InChiKey: HSBNFMOVXDDRMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-ethoxy-3-(4-((2-methylbenzyl)oxy)phenyl)propanoate 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 7.0h， 生成 3-ethoxy-3-{4-[(2-methylbenzyl)oxy]phenyl}-N-(methylsulfonyl)propaneamide
  参考文献：
  名称：

  Optimization of 3-aryl-3-ethoxypropanoic acids and discovery of the potent GPR40 agonist DS-1558

  摘要：

  GPR40 agonists stimulate insulin secretion only under the presence of high glucose concentration. Based on this mechanism, GPR40 agonists are believed to be promising novel insulin secretagogues with low risk of hypoglycemia. The optimizations of 3-aryl-3-ethoxypropanoic acids were performed to improve in vitro activity. We discovered compound 29r (DS-1558), (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, which was confirmed to have an enhancing effect on glucose-dependent insulin secretion after intravenous glucose injection in SD rats. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.028
• 作为产物：
  描述：

  2-甲基苄溴 在 caesium carbonate 、 silver(l) oxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.83h， 生成 ethyl 3-ethoxy-3-(4-((2-methylbenzyl)oxy)phenyl)propanoate
  参考文献：
  名称：

  CARBOXYLIC ACID COMPOUND

  摘要：

  寻找具有优异活性和安全性的治疗剂和/或预防剂，用于糖尿病或类似疾病。以下通用式（I）所代表的化合物，或其药理学上可接受的盐。在该式中，X代表 ═C(R5)- 或 ═N—；Y代表 —O— 或 —NH—；L代表键或可替代的C1-C3烷基链；M代表可替代的C3-C10环烷基，可替代的C6-C10芳基，或可替代的杂环基；R1代表C1-C6烷基，C3-C10环烷基，C1-C6卤代烷基，C2-C6烯基，C2-C6炔基，C1-C6脂肪酰基，C1-C6烷氧基C1-C6烷基，或C6-C10芳基；而R2、R3、R4和R5可以相同也可以不同，每个代表氢原子，卤原子，C1-C3烷基，C1-C3卤代烷基，C1-C3烷氧基，或硝基。在这种情况下，R1和R2的烷基基团可以结合在一起形成含有一个氧原子的5-至6-成员杂环环。

  公开号：

  US20110053974A1

文献信息

• Palladium-catalyzed Intermolecular Alkoxy-alkoxycarbonylation of Vinylphenols in the Presence of Copper Salt: Unexpected Cooperative Effect of Tin Salt
  作者：Nga Hang Thi Phan、Tomoki Furuya、Takahiro Soeta、Yutaka Ukaji

  DOI：10.1246/cl.160804

  日期：2016.12.5

  Palladium-catalyzed intermolecular alkoxy-alkoxycarbonylation of vinylphenols under normal pressure of CO and O2 in alcohol was developed to afford the corresponding 3-alkoxy-3-arylpropanoates in good to high yields. Not only primary alcohols but also secondary alcohols were applicable to the present reaction. The presence of a tin salt was crucial to realize reproducibly high yields.

  在常压CO和O2的醇中钯催化乙烯基苯酚的分子间烷氧基-烷氧基羰基化得到相应的3-烷氧基-3-芳基丙酸酯，收率良好至高。不仅伯醇而且仲醇都适用于本反应。锡盐的存在对于实现可重复的高产率至关重要。
• CARBOXYLIC ACID COMPOUND
  申请人：TODA Narihiro

  公开号：US20110053974A1

  公开（公告）日：2011-03-03

  To find a therapeutic agent and/or a preventive agent for diabetes mellitus or the like having excellent activity and safety. A compound represented by the following general formula (I), or a pharmacologically acceptable salt thereof. In the formula, X represents ═C(R5)- or ═N—; Y represents —O— or —NH—; L represents a bond or a substitutable C1-C3 alkylene group; M represents a substitutable C3-C10 cycloalkyl group, a substitutable C6-C10 aryl group, or a substitutable heterocyclic group; R 1 represents a C1-C6 alkyl group, a C3-C10 cycloalkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 aliphatic acyl group, a C1-C6 alkoxy C1-C6 alkyl group, or a C6-C10 aryl group; and R 2 , R 3 , R 4 , and R 5 may be the same or different and each represent a hydrogen atom, a halogen atom, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, or a nitro group. In this connection, the alkyl group moieties of R 1 and R 2 may be bonded to each other to form a 5- to 6-membered heterocyclic ring containing one oxygen atom.

  寻找具有优异活性和安全性的治疗剂和/或预防剂，用于糖尿病或类似疾病。以下通用式（I）所代表的化合物，或其药理学上可接受的盐。在该式中，X代表 ═C(R5)- 或 ═N—；Y代表 —O— 或 —NH—；L代表键或可替代的C1-C3烷基链；M代表可替代的C3-C10环烷基，可替代的C6-C10芳基，或可替代的杂环基；R1代表C1-C6烷基，C3-C10环烷基，C1-C6卤代烷基，C2-C6烯基，C2-C6炔基，C1-C6脂肪酰基，C1-C6烷氧基C1-C6烷基，或C6-C10芳基；而R2、R3、R4和R5可以相同也可以不同，每个代表氢原子，卤原子，C1-C3烷基，C1-C3卤代烷基，C1-C3烷氧基，或硝基。在这种情况下，R1和R2的烷基基团可以结合在一起形成含有一个氧原子的5-至6-成员杂环环。
• Discovery of 3-aryl-3-ethoxypropanoic acids as orally active GPR40 agonists
  作者：Rieko Takano、Masao Yoshida、Masahiro Inoue、Takeshi Honda、Ryutaro Nakashima、Koji Matsumoto、Tatsuya Yano、Tsuneaki Ogata、Nobuaki Watanabe、Narihiro Toda

  DOI：10.1016/j.bmcl.2014.04.065

  日期：2014.7

  The G protein-coupled receptor 40 (GPR40) mediates enhancement of glucose-stimulated insulin secretion in pancreatic 0 cells. The GPR40 agonist has been attracting attention as a novel insulin secretagogue with glucose dependency for the treatment of type 2 diabetes. The optimization study of compound 1 led to a potent and bioavailable GPR40 agonist 24, which showed insulin secretion and glucose lowering effects in rat OGTT. Compound 24 is a potential lead compound for a novel insulin secretagogue with a low risk of hypoglycemia. (C) 2014 Elsevier Ltd. All rights reserved.
• US8222281B2
  申请人：——

  公开号：US8222281B2

  公开（公告）日：2012-07-17
• Optimization of 3-aryl-3-ethoxypropanoic acids and discovery of the potent GPR40 agonist DS-1558
  作者：Rieko Takano、Masao Yoshida、Masahiro Inoue、Takeshi Honda、Ryutaro Nakashima、Koji Matsumoto、Tatsuya Yano、Tsuneaki Ogata、Nobuaki Watanabe、Masakazu Hirouchi、Takako Kimura、Narihiro Toda

  DOI：10.1016/j.bmc.2015.07.028

  日期：2015.9

  GPR40 agonists stimulate insulin secretion only under the presence of high glucose concentration. Based on this mechanism, GPR40 agonists are believed to be promising novel insulin secretagogues with low risk of hypoglycemia. The optimizations of 3-aryl-3-ethoxypropanoic acids were performed to improve in vitro activity. We discovered compound 29r (DS-1558), (3S)-3-ethoxy-3-(4-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, which was confirmed to have an enhancing effect on glucose-dependent insulin secretion after intravenous glucose injection in SD rats. (C) 2015 Elsevier Ltd. All rights reserved.