4-(5-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-yl)phenyl N,N-diethylcarbamate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 4-(5-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-yl)phenyl N,N-diethylcarbamate
• 英文别名: N,N-diethylcarbamic acid 4-(5-hydroxy-6,7-dimethoxy-4-oxo-4H-1-benzopyran-2-yl)phenyl ester；4-(5-hydroxy-6,7-dimethoxy-4-oxo-4h-chromen-2-yl)phenyl N,N-diethylcarbamate；[4-(5-hydroxy-6,7-dimethoxy-4-oxochromen-2-yl)phenyl] N,N-diethylcarbamate
• 化学式: C₂₂H₂₃NO₇
• 分子量: 413.427
• InChiKey: BCPMGKFDBYFFIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  94.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,3,4-三甲氧基-6-羟基苯乙酮 在 盐酸 、 4-二甲氨基吡啶 、 aluminum (III) chloride 、 硫酸 、 水 、 potassium carbonate 、 potassium iodide 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 73.67h， 生成 4-(5-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-yl)phenyl N,N-diethylcarbamate
  参考文献：
  名称：

  Multifunctional scutellarin–rivastigmine hybrids with cholinergic, antioxidant, biometal chelating and neuroprotective properties for the treatment of Alzheimer’s disease

  摘要：

  To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed ligand strategy. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metal-chelating properties and neuroprotective effects against hydrogen peroxide induced PC12 cell injury were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good multifunctional activities. In particular, compound 15c exhibited dual inhibitory potency on acetylcholinesterase and butyrylcholinesterase with IC50 values of 0.57 and 22.6 mu M, respectively, and good antioxidative activity, with a value 1.3-fold of Trolox. In addition, 15c acted as a selective biometal chelator and possessed neuroprotective effects. Furthermore, 15c could cross the blood-brain barrier (BBB) in vitro and had significant neuroprotective effects in scopolamine-induced cognitive impairment in mice. Taken together, these results suggest that compound 15c might be a potential multifunctional agent for the treatment of AD. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.005

文献信息

• Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease
  作者：Zhi-pei Sang、Xiao-ming Qiang、Yan Li、Bei Wu、Hui Zhang、Ming-gao Zhao、Yong Deng

  DOI：10.1111/cbdd.12580

  日期：2015.11

  A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget‐directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide‐induced PC12 cell injury were evaluated in vitro. The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 ± 0.03 μm and 22.1 ± 0.15 μm, respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step‐down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent against AD.
• Multifunctional scutellarin–rivastigmine hybrids with cholinergic, antioxidant, biometal chelating and neuroprotective properties for the treatment of Alzheimer’s disease
  作者：Zhipei Sang、Yan Li、Xiaoming Qiang、Ganyuan Xiao、Qiang Liu、Zhenghuai Tan、Yong Deng

  DOI：10.1016/j.bmc.2015.01.005

  日期：2015.2

  To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed ligand strategy. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metal-chelating properties and neuroprotective effects against hydrogen peroxide induced PC12 cell injury were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good multifunctional activities. In particular, compound 15c exhibited dual inhibitory potency on acetylcholinesterase and butyrylcholinesterase with IC50 values of 0.57 and 22.6 mu M, respectively, and good antioxidative activity, with a value 1.3-fold of Trolox. In addition, 15c acted as a selective biometal chelator and possessed neuroprotective effects. Furthermore, 15c could cross the blood-brain barrier (BBB) in vitro and had significant neuroprotective effects in scopolamine-induced cognitive impairment in mice. Taken together, these results suggest that compound 15c might be a potential multifunctional agent for the treatment of AD. (c) 2015 Elsevier Ltd. All rights reserved.