7-(2-((1-benzylpiperidin-4-yl)amino)ethoxy)-3-chloro-4-methyl-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 7-(2-((1-benzylpiperidin-4-yl)amino)ethoxy)-3-chloro-4-methyl-2H-chromen-2-one
• 英文别名: 7-[2-[(1-Benzylpiperidin-4-yl)amino]ethoxy]-3-chloro-4-methylchromen-2-one；7-[2-[(1-benzylpiperidin-4-yl)amino]ethoxy]-3-chloro-4-methylchromen-2-one
• 化学式: C₂₄H₂₇ClN₂O₃
• 分子量: 426.943
• InChiKey: UUZIPHVUUZOBHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氯-7-羟基-4-甲基香豆素 在 potassium carbonate 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 12.0h， 生成 7-(2-((1-benzylpiperidin-4-yl)amino)ethoxy)-3-chloro-4-methyl-2H-chromen-2-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel donepezil–coumarin hybrids as multi-target agents for the treatment of Alzheimer’s disease

  摘要：

  Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 mu M and 0.93 mu M, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 mu M for hAChE; 1.98 mu M for hBuChE; 2.62 mu M for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.02.023

文献信息

• Design, synthesis and biological evaluation of novel donepezil–coumarin hybrids as multi-target agents for the treatment of Alzheimer’s disease
  作者：Sai-Sai Xie、Jin-Shuai Lan、Xiaobing Wang、Zhi-Min Wang、Neng Jiang、Fan Li、Jia-Jia Wu、Jin Wang、Ling-Yi Kong

  DOI：10.1016/j.bmc.2016.02.023

  日期：2016.4

  Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 mu M and 0.93 mu M, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 mu M for hAChE; 1.98 mu M for hBuChE; 2.62 mu M for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. (C) 2016 Elsevier Ltd. All rights reserved.