methyl 3-(4-ethynyl-2-fluorophenyl)propanoate | 1402601-93-7

• 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: methyl 3-(4-ethynyl-2-fluorophenyl)propanoate
• 英文别名: Methyl 3-(4-ethynyl-2-fluorophenyl)propanoate
• CAS: 1402601-93-7
• 化学式: C₁₂H₁₁FO₂
• 分子量: 206.217
• InChiKey: QQWZWUSBRURTJV-UHFFFAOYSA-N

物化性质

• 沸点：
  269.0±35.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-ethynyl-2-fluorophenyl)propanoate 在 copper(l) iodide 、 sodium tetrachloropalladate(II) 、 四甲基乙二胺 、 lithium hydroxide 、 2-二叔丁基膦-1-苯基吲哚 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-(4-((3,5-dichlorophenyl)ethynyl)-2-fluorophenyl)propanoic acid
  参考文献：
  名称：

  Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes

  摘要：

  Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic beta-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing.

  DOI：

  10.1021/ml4000673
• 作为产物：
  描述：

  ethyl (E)-3-(4-bromo-2-fluorophenyl)acrylate 在 sodium tetrahydroborate 、 copper(l) iodide 、 sodium tetrachloropalladate(II) 、 四甲基乙二胺 、 potassium carbonate 、 cobalt(II) chloride 、 2-二叔丁基膦-1-苯基吲哚 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成 methyl 3-(4-ethynyl-2-fluorophenyl)propanoate
  参考文献：
  名称：

  Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes

  摘要：

  Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic beta-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing.

  DOI：

  10.1021/ml4000673

文献信息

• [EN] ORTHO-FLUORO SUBSTITUTED COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES<br/>[FR] COMPOSÉS ORTHO-FLUORO SUBSTITUÉS POUR TRAITER LES MALADIES MÉTABOLIQUES
  申请人：UNIV SYDDANSK

  公开号：WO2012136221A1

  公开（公告）日：2012-10-11

  There is provided novel fluoro-substituted 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 II diabetes, hypertension, ketoacidosis, obesity, glucose intolerance, and hypercholesterolemia and related disorders associated with abnormally high or low plasma lipoprotein, triglyceride or glucose levels.

  提供了一种新颖的氟取代化合物，能够调节G-蛋白偶联受体GPR40，包括这些化合物的组合物，以及它们在体内控制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、葡萄糖耐量不良、高胆固醇血症以及与异常高或低血浆脂蛋白、甘油三酯或葡萄糖水平相关的疾病的方法。
• ORTHO-FLUORO SUBSTITUTED COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES
  申请人：Ulven Trond

  公开号：US20140058125A1

  公开（公告）日：2014-02-27

  There is provided novel fluoro-substituted 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 II diabetes, hypertension, ketoacidosis, obesity, glucose intolerance, and hypercholesterolemia and related disorders associated with abnormally high or low plasma lipoprotein, triglyceride or glucose levels.

  本发明提供了一种新型的氟取代化合物，能够调节G蛋白偶联受体GPR40，包括该化合物的组合物，以及其使用方法，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、葡萄糖不耐受症和与异常高或低的血浆脂蛋白、甘油三酯或葡萄糖水平相关的疾病。
• Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area, and Robust in Vivo Efficacy
  作者：Steffen V. F. Hansen、Elisabeth Christiansen、Christian Urban、Brian D. Hudson、Claire J. Stocker、Maria E. Due-Hansen、Ed T. Wargent、Bharat Shimpukade、Reinaldo Almeida、Christer S. Ejsing、Michael A. Cawthorne、Matthias U. Kassack、Graeme Milligan、Trond Ulven

  DOI：10.1021/acs.jmedchem.5b01962

  日期：2016.3.24

  The free fatty acid receptor 1 (FFA1 or GPR40) is established as an interesting potential target for treatment of type 2 diabetes. However, to obtain optimal ligands, it may be necessary to limit both lipophilicity and polar surface area, translating to a need for small compounds. We here describe the identification of 24, a potent FFA1 agonist with low lipophilicity and very high ligand efficiency that exhibit robust glucose lowering effect.
• US9499467B2
  申请人：——

  公开号：US9499467B2

  公开（公告）日：2016-11-22
• Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes
  作者：Elisabeth Christiansen、Steffen V. F. Hansen、Christian Urban、Brian D. Hudson、Edward T. Wargent、Manuel Grundmann、Laura Jenkins、Mohamed Zaibi、Claire J. Stocker、Susanne Ullrich、Evi Kostenis、Matthias U. Kassack、Graeme Milligan、Michael A. Cawthorne、Trond Ulven

  DOI：10.1021/ml4000673

  日期：2013.5.9

  Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic beta-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing.