3-ethoxy-3-{4-[(4-fluoronaphthalen-1-yl)methoxy]phenyl}propanoic acid | 1202575-81-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-ethoxy-3-{4-[(4-fluoronaphthalen-1-yl)methoxy]phenyl}propanoic acid
• 英文别名: 3-Ethoxy-3-{4-[(4-fluoro-1-naphthyl)methoxy]phenyl}propionic acid；3-Ethoxy-3-[4-[(4-fluoronaphthalen-1-yl)methoxy]phenyl]propanoic acid
• CAS: 1202575-81-2
• 化学式: C₂₂H₂₁FO₄
• 分子量: 368.405
• InChiKey: KCFOERATBKMTCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 3-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-hydroxypropionate 在 四丁基氟化铵 、 三苯基膦 、 sodium hydroxide 、 silver(l) oxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 反应 15.0h， 生成 3-ethoxy-3-{4-[(4-fluoronaphthalen-1-yl)methoxy]phenyl}propanoic acid
  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

文献信息

• 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。
• 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.