2-(4-Benzo[1,3]dioxol-5-yl-3-fluoro-phenyl)-propionic 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: 2-(4-Benzo[1,3]dioxol-5-yl-3-fluoro-phenyl)-propionic acid
• 英文别名: 2-[4-(1,3-benzodioxol-5-yl)-3-fluorophenyl]propanoic acid
• 化学式: C₁₆H₁₃FO₄
• 分子量: 288.275
• InChiKey: ARDDKEOZWWELGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-[(3-氟-4-硝基苯基)甲基]丙二酸二乙基酯 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 四(三苯基膦)钯 、 氢气 、 sodium carbonate 、 sodium nitrite 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 12.0h， 生成 2-(4-Benzo[1,3]dioxol-5-yl-3-fluoro-phenyl)-propionic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of Flurbiprofen Analogues as Selective Inhibitors of β-Amyloid_1-42 Secretion

  摘要：

  Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit beta-amyloid(1-42) (A beta 42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing A beta 42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on A beta 42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma A beta 42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.

  DOI：

  10.1021/jm0502541