2-(2-fluoro-4'-trifluoromethylbiphenyl-4-yl)-N-hydroxypropionamidine | 884905-31-1

• 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: 2-(2-fluoro-4'-trifluoromethylbiphenyl-4-yl)-N-hydroxypropionamidine
• 英文别名: 2-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]-N'-hydroxypropanimidamide
• CAS: 884905-31-1
• 化学式: C₁₆H₁₄F₄N₂O
• 分子量: 326.294
• InChiKey: KIBSJDLLNFTSAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-fluoro-4'-trifluoromethylbiphenyl-4-yl)-N-hydroxypropionamidine 、 N,N'-羰基二咪唑 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以125 mg的产率得到3-[1-(2-Fluoro-4'-trifluoromethyl-biphenyl-4-yl)-ethyl]-4H-[1,2,4]oxadiazol-5-one
  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
• 作为产物：
  描述：

  2-(2-fluoro-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)propionic acid 在 吡啶 、 草酰氯 、 盐酸羟胺 、 氨 、 碳酸氢钠 、 三氟乙酸酐 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 8.5h， 生成 2-(2-fluoro-4'-trifluoromethylbiphenyl-4-yl)-N-hydroxypropionamidine
  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