2-[2-(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl-amino)ethyl]amino-1,4-naphthoquinone | 1631758-83-2

• 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: 2-[2-(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl-amino)ethyl]amino-1,4-naphthoquinone
• 英文别名: 2-[[2-[(1,2,3,4-Tetrahydro-7-methoxy-9-acridinyl)amino]ethyl]amino]-1,4-naphthalenedione；2-[2-[(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl)amino]ethylamino]naphthalene-1,4-dione
• CAS: 1631758-83-2
• 化学式: C₂₆H₂₅N₃O₃
• 分子量: 427.503
• InChiKey: RKAZYMSLCDWTKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  9-chloro-7-methoxy-1,2,3,4-tetrahydroacridine 以 二氯甲烷 、 苯酚 为溶剂， 反应 12.67h， 生成 2-[2-(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl-amino)ethyl]amino-1,4-naphthoquinone
  参考文献：
  名称：

  Multitarget Drug Design Strategy: Quinone–Tacrine Hybrids Designed To Block Amyloid-β Aggregation and To Exert Anticholinesterase and Antioxidant Effects

  摘要：

  We report the identification of multitarget anti-Alzheimer compounds designed by combining a naphthoquinone function and a tacrine fragment. In vitro, 15 compounds displayed excellent acetylcholinesterase (AChE) inhibitory potencies and interesting capabilities to block amyloid-beta (A beta) aggregation. The X-ray analysis of one of those compounds in complex with AChE allowed rationalizing the outstanding activity data (IC50 = 0.72 nM). Two of the compounds showed negligible toxicity in immortalized mouse cortical neurons Neuro2A and primary rat cerebellar granule neurons. However, only one of them was less hepatotoxic than tacrine in HepG2 cells. In T67 cells, both compounds showed antioxidant activity, following NQO1 induction. Furthermore, in Neuro2A, they were able to completely revert the decrease in viability induced by A beta. Importantly, they crossed the blood-brain barrier, as demonstrated in ex vivo experiments with rats. When ex vivo results were combined with in vitro studies, these two compounds emerged to be promising multitarget lead candidates worthy of further pursuit.

  DOI：

  10.1021/jm5010804

文献信息

• Multitarget Drug Design Strategy: Quinone–Tacrine Hybrids Designed To Block Amyloid-β Aggregation and To Exert Anticholinesterase and Antioxidant Effects
  作者：Eugenie Nepovimova、Elisa Uliassi、Jan Korabecny、Luis Emiliano Peña-Altamira、Sarah Samez、Alessandro Pesaresi、Gregory E. Garcia、Manuela Bartolini、Vincenza Andrisano、Christian Bergamini、Romana Fato、Doriano Lamba、Marinella Roberti、Kamil Kuca、Barbara Monti、Maria Laura Bolognesi

  DOI：10.1021/jm5010804

  日期：2014.10.23

  We report the identification of multitarget anti-Alzheimer compounds designed by combining a naphthoquinone function and a tacrine fragment. In vitro, 15 compounds displayed excellent acetylcholinesterase (AChE) inhibitory potencies and interesting capabilities to block amyloid-beta (A beta) aggregation. The X-ray analysis of one of those compounds in complex with AChE allowed rationalizing the outstanding activity data (IC50 = 0.72 nM). Two of the compounds showed negligible toxicity in immortalized mouse cortical neurons Neuro2A and primary rat cerebellar granule neurons. However, only one of them was less hepatotoxic than tacrine in HepG2 cells. In T67 cells, both compounds showed antioxidant activity, following NQO1 induction. Furthermore, in Neuro2A, they were able to completely revert the decrease in viability induced by A beta. Importantly, they crossed the blood-brain barrier, as demonstrated in ex vivo experiments with rats. When ex vivo results were combined with in vitro studies, these two compounds emerged to be promising multitarget lead candidates worthy of further pursuit.