methyl 2-[4'-(3-bromopropoxy)-2-fluorobiphenyl-4-yl]propanoate | 1430219-48-9

• 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: methyl 2-[4'-(3-bromopropoxy)-2-fluorobiphenyl-4-yl]propanoate
• CAS: 1430219-48-9
• 化学式: C₁₉H₂₀BrFO₃
• 分子量: 395.268
• InChiKey: UFBNGGUSYVFQPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.93
• 重原子数：
  24.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl 2-[4'-(3-bromopropoxy)-2-fluorobiphenyl-4-yl]propanoate 在 lithium hydroxide monohydrate 、 silver nitrate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 30.0h， 生成 2-{2-fluoro-4'-[3-(nitrooxy)propoxy]biphenyl-4-yl}propanoic acid
  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 、 硫酸 、 potassium carbonate 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 62.0h， 生成 methyl 2-[4'-(3-bromopropoxy)-2-fluorobiphenyl-4-yl]propanoate
  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

文献信息

• NO-donating tacrine derivatives as potential butyrylcholinesterase inhibitors with vasorelaxation activity
  作者：Yao Chen、Jianfei Sun、Zhangjian Huang、Hong Liao、Sixun Peng、Jochen Lehmann、Yihua Zhang

  DOI：10.1016/j.bmcl.2013.04.008

  日期：2013.6

  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.