2-(4-(5-((2-oxo-4-phenyl-2H-chromen-7-yl)oxy)pentyl)piperazin-1-yl)-N-(1,2,3,4-tetrahydroacridin-9-yl)acetamide

• 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: 2-(4-(5-((2-oxo-4-phenyl-2H-chromen-7-yl)oxy)pentyl)piperazin-1-yl)-N-(1,2,3,4-tetrahydroacridin-9-yl)acetamide
• 英文别名: 2-[4-[5-(2-oxo-4-phenylchromen-7-yl)oxypentyl]piperazin-1-yl]-N-(1,2,3,4-tetrahydroacridin-9-yl)acetamide
• 化学式: C₃₉H₄₂N₄O₄
• 分子量: 630.787
• InChiKey: CTGCJJGSKOQITO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  7-羟基-4-苯基香豆素 在 potassium carbonate 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 12.0h， 生成 2-(4-(5-((2-oxo-4-phenyl-2H-chromen-7-yl)oxy)pentyl)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