3-chloro-4-methyl-7-(2-(4-(3-((1,2,3,4-tetrahydroacridin-9-yl)amino)propyl)piperazin-1-yl)ethoxy)-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-chloro-4-methyl-7-(2-(4-(3-((1,2,3,4-tetrahydroacridin-9-yl)amino)propyl)piperazin-1-yl)ethoxy)-2H-chromen-2-one
• 英文别名: 3-Chloro-4-methyl-7-[2-[4-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]piperazin-1-yl]ethoxy]chromen-2-one；3-chloro-4-methyl-7-[2-[4-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]piperazin-1-yl]ethoxy]chromen-2-one
• 化学式: C₃₂H₃₇ClN₄O₃
• 分子量: 561.124
• InChiKey: GDFJHAWHVPWSSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  7

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 3-chloro-4-methyl-7-(2-(4-(3-((1,2,3,4-tetrahydroacridin-9-yl)amino)propyl)piperazin-1-yl)ethoxy)-2H-chromen-2-one
  参考文献：
  名称：

  Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2015.03.040

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.