methyl 3-(4-((3-(trifluoromethoxy)-phenyl)ethynyl)phenyl)propanoate | 1207950-04-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 3-(4-((3-(trifluoromethoxy)-phenyl)ethynyl)phenyl)propanoate
• 英文别名: Methyl 3-[4-[2-[3-(trifluoromethoxy)phenyl]ethynyl]phenyl]propanoate
• CAS: 1207950-04-6
• 化学式: C₁₉H₁₅F₃O₃
• 分子量: 348.322
• InChiKey: DZZCNHBHRPNKHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-((3-(trifluoromethoxy)-phenyl)ethynyl)phenyl)propanoate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 以94%的产率得到3-[4-[2-[3-(Trifluoromethoxy)phenyl]ethynyl]phenyl]propanoic acid
  参考文献：
  名称：

  Discovery of a Potent and Selective Free Fatty Acid Receptor 1 Agonist with Low Lipophilicity and High Oral Bioavailability

  摘要：

  The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.

  DOI：

  10.1021/jm301470a
• 作为产物：
  描述：

  3-三氟甲氧基溴苯 、 3-(4-乙炔基苯基)丙酸甲酯 在 copper(l) iodide 、 sodium tetrachloropalladate(II) 、 2-二叔丁基膦-1-苯基吲哚 作用下， 以 2,3-二甲基-2,3-丁二胺 、 水 为溶剂， 以87%的产率得到methyl 3-(4-((3-(trifluoromethoxy)-phenyl)ethynyl)phenyl)propanoate
  参考文献：
  名称：

  A Rapid and Efficient Sonogashira Protocol and Improved Synthesis of Free Fatty Acid 1 (FFA1) Receptor Agonists

  摘要：

  A protocol for rapid and efficient Pd/Cu-catalyzed coupling of aryl bromides and iodides to terminal alkynes has been developed with use of 2-(di-tert-butylphosphino)-N-phenylindole (cataCXium PIntB) as ligand in TMEDA and water. The new protocol successfully couples substrates which failed with standard Sonogashira conditions, and enables an efficient general synthetic route to free fatty acid 1 (FFA1) receptor ligands from 3-(4-bromophenyl)-propionic acid.

  DOI：

  10.1021/jo902533p

文献信息

• Discovery of a Potent and Selective Free Fatty Acid Receptor 1 Agonist with Low Lipophilicity and High Oral Bioavailability
  作者：Elisabeth Christiansen、Maria E. Due-Hansen、Christian Urban、Manuel Grundmann、Johannes Schmidt、Steffen V. F. Hansen、Brian D. Hudson、Mohamed Zaibi、Stine B. Markussen、Ellen Hagesaether、Graeme Milligan、Michael A. Cawthorne、Evi Kostenis、Matthias U. Kassack、Trond Ulven

  DOI：10.1021/jm301470a

  日期：2013.2.14

  The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.
• A Rapid and Efficient Sonogashira Protocol and Improved Synthesis of Free Fatty Acid 1 (FFA1) Receptor Agonists
  作者：Elisabeth Christiansen、Maria E. Due-Hansen、Trond Ulven

  DOI：10.1021/jo902533p

  日期：2010.2.19

  A protocol for rapid and efficient Pd/Cu-catalyzed coupling of aryl bromides and iodides to terminal alkynes has been developed with use of 2-(di-tert-butylphosphino)-N-phenylindole (cataCXium PIntB) as ligand in TMEDA and water. The new protocol successfully couples substrates which failed with standard Sonogashira conditions, and enables an efficient general synthetic route to free fatty acid 1 (FFA1) receptor ligands from 3-(4-bromophenyl)-propionic acid.