3-[4-[2-(4-Chloro-2-methylphenyl)ethynyl]phenyl]propanoic acid | 1420836-54-9

• 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-(4-Chloro-2-methylphenyl)ethynyl]phenyl]propanoic acid
• 英文别名: 3-[4-[2-(4-chloro-2-methylphenyl)ethynyl]phenyl]propanoic acid
• CAS: 1420836-54-9
• 化学式: C₁₈H₁₅ClO₂
• 分子量: 298.769
• InChiKey: OKUIEMYUMHZGAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  methyl 3-(4-((4-chloro-2-methylphenyl)ethynyl)phenyl)-propanoate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 以99%的产率得到3-[4-[2-(4-Chloro-2-methylphenyl)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

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.