TUG-469 | 1236109-67-3

• 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: TUG-469
• 英文别名: 3-(4-(((2'-Methyl-[1,1'-biphenyl]-3-yl)methyl)amino)phenyl)propanoic acid；3-[4-[[3-(2-methylphenyl)phenyl]methylamino]phenyl]propanoic acid
• CAS: 1236109-67-3
• 化学式: C₂₃H₂₃NO₂
• 分子量: 345.441
• InChiKey: RUPXKSLKGSSZCP-UHFFFAOYSA-N

物化性质

• 熔点：
  >158°C (dec.)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲基联苯-3-甲醛 、 3-(4-氨基苯基)丙酸 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 生成 TUG-469
  参考文献：
  名称：

  Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists: Mesylpropoxy Appendage Lowers Lipophilicity and Improves ADME Properties

  摘要：

  FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on S. The appendage significantly lowers lipophilicity and improves metabolic stability while preserving potency, resulting in discovery of the potent FFA1 agonist 13.

  DOI：

  10.1021/jm3002026

文献信息

• NOVEL HETEROCYCLIC COMPOUNDS
  申请人：CADILA HEALTHCARE LIMITED

  公开号：US20160257701A1

  公开（公告）日：2016-09-08

  The present invention relates to novel GPR 40 agonists of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

  本发明涉及一种新的GPR 40激动剂，其通式为（I），它们的互变异构体，立体异构体，药学上可接受的盐，包含它们的制药组合物，制备它们的方法，这些化合物在医学上的使用以及其制备中涉及的中间体。
• Heterocyclic compounds
  申请人：CADILA HEALTHCARE LIMITED

  公开号：US10011609B2

  公开（公告）日：2018-07-03

  The present invention relates to novel GPR 40 agonists of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

  本发明涉及通式（I）的新型 GPR 40 激动剂、它们的同分异构体、它们的立体异构体、它们的药学上可接受的盐、含有它们的药物组合物、它们的制备方法、这些化合物在医学中的用途以及制备它们所涉及的中间体。
• [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。
• Structure−Activity Study of Dihydrocinnamic Acids and Discovery of the Potent FFA1 (GPR40) Agonist TUG-469
  作者：Elisabeth Christiansen、Maria E. Due-Hansen、Christian Urban、Nicole Merten、Michael Pfleiderer、Kasper K. Karlsen、Sanne S. Rasmussen、Mette Steensgaard、Alexandra Hamacher、Johannes Schmidt、Christel Drewke、Rasmus Koefoed Petersen、Karsten Kristiansen、Susanne Ullrich、Evi Kostenis、Matthias U. Kassack、Trond Ulven

  DOI：10.1021/ml100106c

  日期：2010.10.14

  The free fatty acid 1 receptor (FFA1 or GPR40), which is highly expressed on pancreatic beta-cells and amplifies glucose-stimulated insulin secretion, has emerged as attractive target for the treatment of type 2 diabetes Several FFA1 agonists containing the para-substituted dihydrocinnamic acid moiety are known. We here present a structure-activity relationship study of this compound family suggesting that the central methyleneoxy linker is preferable for the smaller compounds whereas the central methyleneamine linker gives higher potency to the larger compounds. The study resulted in the discovery of the potent and selective full FFA1 agonist TUG-469 (29).
• Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists: Mesylpropoxy Appendage Lowers Lipophilicity and Improves ADME Properties
  作者：Elisabeth Christiansen、Maria E. Due-Hansen、Christian Urban、Manuel Grundmann、Ralf Schröder、Brian D. Hudson、Graeme Milligan、Michael A. Cawthorne、Evi Kostenis、Matthias U. Kassack、Trond Ulven

  DOI：10.1021/jm3002026

  日期：2012.7.26

  FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on S. The appendage significantly lowers lipophilicity and improves metabolic stability while preserving potency, resulting in discovery of the potent FFA1 agonist 13.