7-(2-bromoethoxy)-4-phenyl-2H-chromen-2-one | 1444415-89-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: 7-(2-bromoethoxy)-4-phenyl-2H-chromen-2-one
• CAS: 1444415-89-7
• 化学式: C₁₇H₁₃BrO₃
• 分子量: 345.192
• InChiKey: UCAXUQVXRDBCRC-UHFFFAOYSA-N

物化性质

• 沸点：
  494.4±45.0 °C(predicted)
• 密度：
  1.481±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  39.44
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(piperazin-1-yl)-N-(1,2,3,4-tetrahydro-acridin-9-yl)acetamide 、 7-(2-bromoethoxy)-4-phenyl-2H-chromen-2-one 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 8.0h， 以56%的产率得到2-(4-(2-((2-oxo-4-phenyl-2H-chromen-7-yl)oxy)ethyl)piperazin-1-yl)-N-(1,2,3,4-tetrahydroacridin-9-yl)acetamide
  参考文献：
  名称：

  Design, synthesis and evaluation of novel tacrine–coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease

  摘要：

  A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced,beta-amyloid (A beta) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 mu M) and A beta aggregation (67.8%, 20 mu M). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 mu M) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.051
• 作为产物：
  描述：

  苯甲酰乙酸乙酯 在 硫酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 8.0h， 生成 7-(2-bromoethoxy)-4-phenyl-2H-chromen-2-one
  参考文献：
  名称：

  Design, synthesis and evaluation of novel tacrine–coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease

  摘要：

  A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced,beta-amyloid (A beta) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 mu M) and A beta aggregation (67.8%, 20 mu M). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 mu M) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.051

文献信息

• Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease
  作者：Sai-Sai Xie、Xiaobing Wang、Neng Jiang、Wenying Yu、Kelvin D.G. Wang、Jin-Shuai Lan、Zhong-Rui Li、Ling-Yi Kong

  DOI：10.1016/j.ejmech.2015.03.040

  日期：2015.5

  A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 mu M). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment. (C) 2015 Elsevier Masson SAS. All rights reserved.
• 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.