2-{2-fluoro-4'-[3-(nitrooxy)propoxy]biphenyl-4-yl}propanoic acid | 1430219-56-9

• 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'-[3-(nitrooxy)propoxy]biphenyl-4-yl}propanoic acid
• CAS: 1430219-56-9
• 化学式: C₁₈H₁₈FNO₆
• 分子量: 363.342
• InChiKey: DPVLGSUNPIBKRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.66
• 重原子数：
  26.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  98.9
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-{2-fluoro-4'-[3-(nitrooxy)propoxy]biphenyl-4-yl}propanoic acid 、 N-(1,2,3,4-tetrahydroacridin-9-yl)octane-1,8-diamine 在 N,N'-二环己基碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 24.5h， 以46%的产率得到3-{2'-fluoro-4'-[1-oxo-1-(8-(1,2,3,4-tetrahydroacridin-9-ylamino)octylamino)propan-2-yl]biphenyl-4-yloxy}propyl nitrate
  参考文献：
  名称：

  Design, synthesis and evaluation of tacrine–flurbiprofen–nitrate trihybrids as novel anti-Alzheimer’s disease agents

  摘要：

  To search for multifunctional anti-Alzheimer's disease (AD) agents with good safety, the previously synthesized tacrine-flurbiprofen hybrids 1a and 1b were modified into tacrine-flurbiprofen-nitrate trihybrids 3a-h. These compounds displayed comparable or higher cholinesterase inhibitory activity relative to the bivalent hybrids. Compound 3a was the most potent, which released moderate NO, exerted blood vessel relaxative activity, and showed significant A beta inhibitory effects whereas tacrine and flurbiprofen did not exhibit any Ab inhibitory activity at the same dose. In addition, 3a was active in improving memory impairment in vivo. More importantly, the hepatotoxicity study showed that 3a was much safer than tacrine, suggesting it might be a promising anti-AD agent for further investigation. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.005
• 作为产物：
  描述：

  氟比洛芬 在 aluminum (III) chloride 、 lithium hydroxide monohydrate 、 硫酸 、 水 、 potassium carbonate 、 silver nitrate 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 86.0h， 生成 2-{2-fluoro-4'-[3-(nitrooxy)propoxy]biphenyl-4-yl}propanoic acid
  参考文献：
  名称：

  NO-donating tacrine derivatives as potential butyrylcholinesterase inhibitors with vasorelaxation activity

  摘要：

  To search for potent anti-Alzheimer's disease (AD) agents with multifunctional effects, 12 NO-donating tacrine-flurbiprofen hybrid compounds (2a-l) were synthesized and biologically evaluated. It was found that all the new target compounds showed selective butyrylcholinesterase (BuChE) inhibitory activity in vitro comparable or higher than tacrine and the tacrine-flurbiprofen hybrid compounds 1a-c, and released moderate amount of NO in vitro. The kinetic study suggests that one of the most active and highest BuChE selective compounds 2d may not only compete with the substrate for the same catalytic active site (CAS) but also interact with a second binding site. Furthermore, 2d and 2l exhibited significant vascular relaxation effect, which is beneficial for the treatment of AD. All the results suggest that 2d and 2l might be promising lead compounds for further research. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.008