3-(4-((2,6-dichloropyridin-4-yl)ethynyl)phenyl)propanoic acid | 1206629-08-4

• 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-(4-((2,6-dichloropyridin-4-yl)ethynyl)phenyl)propanoic acid
• 英文别名: TUG-499；3-[4-[2-(2,6-Dichloropyridin-4-yl)ethynyl]phenyl]propanoic acid
• CAS: 1206629-08-4
• 化学式: C₁₆H₁₁Cl₂NO₂
• 分子量: 320.175
• InChiKey: GCWBKYDSSJIRNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl 3-(4-((2,6-dichloropyridin-4-yl)ethynyl)phenyl)-propanoate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 以99%的产率得到3-(4-((2,6-dichloropyridin-4-yl)ethynyl)phenyl)propanoic acid
  参考文献：
  名称：

  Identification of a Potent and Selective Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist with Favorable Physicochemical and in Vitro ADME Properties

  摘要：

  The free fatty acid receptor 1 (FFA1, also known as GPR40) enhances glucose-stimulated insulin secretion from pancreatic beta-cells and is recognized as an interesting new target for treatment of type 2 diabetes. Several series of selective FFA1 agonists are already known. Most of these are derived from free fatty acids (FFAs) or glitazones and are relatively lipophilic. Aiming for the development of potent, selective, and less lipophilic FFA1 agonists, the terminal phenyl of a known compound series was replaced by nitrogen containing heterocycles. This resulted in the identification of 37, a selective FFA1 agonist with potent activity on recombinant human FFA1 receptors and on the rat insulinoma cell line INS-1E, optimal lipophilicity, and excellent in vitro permeability and metabolic stability.

  DOI：

  10.1021/jm2005699

文献信息

• [EN] COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES<br/>[FR] COMPOSÉS DESTINÉS AU TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：UNIV SYDDANSK

  公开号：WO2010012650A1

  公开（公告）日：2010-02-04

  There is provided novel compounds capable of modulating the G-protein-coupled receptor GPR40, compositions comprising the compounds, and methods for their use for controlling insulin levels in vivo and for the treatment of conditions such as type Il diabetes, hypertension, ketoacidosis, obesity, glucose intolerance, and hypercholesterolemia and related disorders associated with abnormally high or low plasma lipoprotein, triglyceride or glucose levels.

  提供了一种新型化合物，能够调节G蛋白偶联受体GPR40，包括该化合物的组合物和使用方法，用于控制体内胰岛素水平，治疗II型糖尿病、高血压、酮症、肥胖症、葡萄糖不耐受症和与异常高或低血浆脂蛋白、甘油三酯或葡萄糖水平相关的相关疾病。
• COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES
  申请人：Ulven Trond

  公开号：US20110152315A1

  公开（公告）日：2011-06-23

  There is provided novel compounds capable of modulating the G-protein-coupled receptor GPR40, compositions comprising the compounds, and methods for their use for controlling insulin levels in vivo and for the treatment of conditions such as type I1 diabetes, hypertension, ketoacidosis, obesity, glucose intolerance, and hypercholesterolemia and related disorders associated with abnormally high or low plasma lipoprotein, triglyceride or glucose levels.

  提供了一种新的化合物，能够调节G蛋白偶联受体GPR40，包括该化合物的组合物以及使用它们的方法，用于控制体内胰岛素水平和治疗诸如2型糖尿病、高血压、酮症酸中毒、肥胖症、葡萄糖耐受性不良以及与异常高或低血浆脂蛋白、甘油三酯或葡萄糖水平有关的相关疾病。
• [EN] PHENYLALANINE COMPOUND HAVING NITROGEN HETEROCYCLIC LINK, PHARMACEUTICAL COMPOSITION THEREOF, PREPARATION METHOD THEREFOR, AND USE THEREOF<br/>[FR] COMPOSÉ DE PHÉNYLALANINE AYANT UN GROUPE DE LIAISON HÉTÉROCYCLIQUE AZOTÉ, COMPOSITION PHARMACEUTIQUE ASSOCIÉE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2014169817A1

  公开（公告）日：2014-10-23

  提供一种具有显著的降血糖和调节糖脂代谢活性的含氮杂环链接的苯丙酸类化合物、其药学上可接受的盐或立体异构体，含有所述化合物的药物组合物，以及所述化合物在制备糖尿病及糖脂代谢紊乱的药物中的用途，尤其是在制备治疗Π型糖尿病药物中的用途。所述化合物具有通式I所示结构。
• US8586607B2
  申请人：——

  公开号：US8586607B2

  公开（公告）日：2013-11-19
• Identification of a Potent and Selective Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist with Favorable Physicochemical and in Vitro ADME Properties
  作者：Elisabeth Christiansen、Christian Urban、Manuel Grundmann、Maria E. Due-Hansen、Ellen Hagesaether、Johannes Schmidt、Leonardo Pardo、Susanne Ullrich、Evi Kostenis、Matthias Kassack、Trond Ulven

  DOI：10.1021/jm2005699

  日期：2011.10.13

  The free fatty acid receptor 1 (FFA1, also known as GPR40) enhances glucose-stimulated insulin secretion from pancreatic beta-cells and is recognized as an interesting new target for treatment of type 2 diabetes. Several series of selective FFA1 agonists are already known. Most of these are derived from free fatty acids (FFAs) or glitazones and are relatively lipophilic. Aiming for the development of potent, selective, and less lipophilic FFA1 agonists, the terminal phenyl of a known compound series was replaced by nitrogen containing heterocycles. This resulted in the identification of 37, a selective FFA1 agonist with potent activity on recombinant human FFA1 receptors and on the rat insulinoma cell line INS-1E, optimal lipophilicity, and excellent in vitro permeability and metabolic stability.