ethyl 3-cyclopropyl-3-(2-methoxypyridin-4-yl)acrylate | 1450931-77-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 3-cyclopropyl-3-(2-methoxypyridin-4-yl)acrylate
• 英文别名: ethyl 3-cyclopropyl-3-(2-methoxypyridin-4-yl)prop-2-enoate
• CAS: 1450931-77-7
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: RXHVGORDPSZLBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-cyclopropyl-3-(2-methoxypyridin-4-yl)acrylate 在 水 、 吡啶盐酸盐 、 溶剂黄146 、 silver carbonate 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.33h， 生成 3-cyclopropyl-3-(2-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)pyridin-4-yl)propanoic acid
  参考文献：
  名称：

  EP2816032

  摘要：

  公开号：
• 作为产物：
  描述：

  2-甲氧基吡啶-4-醛 在 三氧化硫吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 1.75h， 生成 ethyl 3-cyclopropyl-3-(2-methoxypyridin-4-yl)acrylate
  参考文献：
  名称：

  EP2816032

  摘要：

  公开号：

文献信息

• AROMATIC RING COMPOUND
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20150045378A1

  公开（公告）日：2015-02-12

  Provided is an aromatic ring compound having a GPR40 agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has a GPR40 agonist activity, and is useful as an agent for the prophylaxis or treatment of diabetes and the like.

  提供了一种具有GPR40激动剂活性的芳香环化合物。式（I）所表示的化合物：其中每个符号如说明中所述，或其盐具有GPR40激动剂活性，并且可用作预防或治疗糖尿病等疾病的药剂。
• Aromatic ring compound
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US09181186B2

  公开（公告）日：2015-11-10

  Provided is an aromatic ring compound having a GPR40 agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has a GPR40 agonist activity, and is useful as an agent for the prophylaxis or treatment of diabetes and the like.

  提供了一种具有GPR40激动剂活性的芳香环化合物。式（I）所表示的化合物：其中每个符号如描述中所述，或其盐具有GPR40激动剂活性，并且可用作预防或治疗糖尿病等疾病的药剂。
• Design and Identification of a GPR40 Full Agonist (<b>SCO-267</b>) Possessing a 2-Carbamoylphenyl Piperidine Moiety
  作者：Hideki Furukawa、Yasufumi Miyamoto、Yasuhiro Hirata、Koji Watanabe、Yuko Hitomi、Yayoi Yoshitomi、Jumpei Aida、Naoyoshi Noguchi、Nobuyuki Takakura、Kazuaki Takami、Seiji Miwatashi、Yoshihiko Hirozane、Teruki Hamada、Ryo Ito、Mitsugi Ookawara、Yusuke Moritoh、Masanori Watanabe、Tsuyoshi Maekawa

  DOI：10.1021/acs.jmedchem.0c00843

  日期：2020.9.24

  GPR40/FFAR1 is a G-protein-coupled receptor expressed in pancreatic beta-cells and enteroendocrine cells. GPR40 activation stimulates secretions of insulin and incretin, both of which are the pivotal regulators of glycemic control. Therefore, a GPR40 agonist is an attractive target for the treatment of type 2 diabetes mellitus. Using the reported biaryl derivative 1, we shifted the hydrophobic moiety to the terminal aryl ring and replaced the central aryl ring with piperidine, generating 2-(4,4-dimethylpentyl)phenyl piperidine 4a, which had improved potency for GPR40 and high lipophilicity. We replaced the hydrophobic moiety with N-alkyl-N-aryl benzamides to lower the lipophilicity and restrict the N-alkyl moieties to the presumed lipophilic pocket using the intramolecular pi-pi stacking of cis-preferential N-alkyl-N-aryl benzamide. Among these, orally available (3S)-3-cyclopropyl-3-(2-((1-(2-((2,2-dimethylpropyl)(6-methylpyridin-2-yl)carbamoyl)-5-methoxyphenyl)piperidin-4-yl)methoxy)pyridin-4-yl)propanoic acid (SCO-267) effectively stimulated insulin secretion and GLP-1 release and ameliorated glucose tolerance in diabetic rats via GPR40 full agonism.