3-(4-((3-(3,5-dimethylisoxazol-4-yl)-5-isobutoxybenzyl)oxy)-2-fluorophenyl)propanoic acid

• 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-((3-(3,5-dimethylisoxazol-4-yl)-5-isobutoxybenzyl)oxy)-2-fluorophenyl)propanoic acid
• 英文别名: 3-[4-[[3-(3,5-Dimethyl-1,2-oxazol-4-yl)-5-(2-methylpropoxy)phenyl]methoxy]-2-fluorophenyl]propanoic acid；3-[4-[[3-(3,5-dimethyl-1,2-oxazol-4-yl)-5-(2-methylpropoxy)phenyl]methoxy]-2-fluorophenyl]propanoic acid
• 化学式: C₂₅H₂₈FNO₅
• 分子量: 441.499
• InChiKey: BJMZEBLXIDSJDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-溴-5-羟基苯甲醛 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 水 、 sodium carbonate 、 potassium carbonate 、 lithium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 42.25h， 生成 3-(4-((3-(3,5-dimethylisoxazol-4-yl)-5-isobutoxybenzyl)oxy)-2-fluorophenyl)propanoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of GPR40/FFAR1 agonists containing 3,5-dimethylisoxazole

  摘要：

  GPR40 is an attractive target due to its glucose-stimulated insulin secretion effect with low risk of causing hypoglycemia, which also can be seen from the clinical studies using TAK-875 (fasiglifam). In the present studies, we discovered a series of analogues containing 3,5-dimethylisoxazole as potent GPR40 agonists, especially compound ilk with an EC50 value of 15.9 nM. Moreover, compound 11k reduced glucose excursion to 23.1% in ICR mice and 29.5% in type 2 diabetic C57BL/6 mice at 30 mg/kg. It also exhibited satisfactory PK profile. Docking studies were conducted to explain the interaction mode of this series. In summary, compound 11k with robust efficacy in vitro and in vivo is a promising drug candidate for further investigation. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.054

文献信息

• Synthesis and biological evaluation of GPR40/FFAR1 agonists containing 3,5-dimethylisoxazole
  作者：Lingyun Yang、Jian Zhang、Lianghui Si、Li Han、Bo Zhang、Hui Ma、Junhao Xing、Leilei Zhao、Jinpei Zhou、Huibin Zhang

  DOI：10.1016/j.ejmech.2016.03.054

  日期：2016.6

  GPR40 is an attractive target due to its glucose-stimulated insulin secretion effect with low risk of causing hypoglycemia, which also can be seen from the clinical studies using TAK-875 (fasiglifam). In the present studies, we discovered a series of analogues containing 3,5-dimethylisoxazole as potent GPR40 agonists, especially compound ilk with an EC50 value of 15.9 nM. Moreover, compound 11k reduced glucose excursion to 23.1% in ICR mice and 29.5% in type 2 diabetic C57BL/6 mice at 30 mg/kg. It also exhibited satisfactory PK profile. Docking studies were conducted to explain the interaction mode of this series. In summary, compound 11k with robust efficacy in vitro and in vivo is a promising drug candidate for further investigation. (C) 2016 Elsevier Masson SAS. All rights reserved.