9-[(2-{4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidin-1-yl}ethyl)amino]-1,2,3,4-tetrahydroacridine | 955993-15-4

• 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: 9-[(2-{4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidin-1-yl}ethyl)amino]-1,2,3,4-tetrahydroacridine
• 英文别名: 5,6-Dimethoxy-2-[[1-[2-(1,2,3,4-tetrahydroacridin-9-ylamino)ethyl]piperidin-4-yl]methyl]-2,3-dihydroinden-1-one
• CAS: 955993-15-4
• 化学式: C₃₂H₃₉N₃O₃
• 分子量: 513.68
• InChiKey: RPCUFCHJHLNWDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-[(2-{4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidin-1-yl}ethyl)amino]-1,2,3,4-tetrahydroacridine 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 9-[(2-{4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidin-1-yl}ethyl)amino]-1,2,3,4-tetrahydroacridine dihydrochloride
  参考文献：
  名称：

  Novel Donepezil-Based Inhibitors of Acetyl- and Butyrylcholinesterase and Acetylcholinesterase-Induced β-Amyloid Aggregation

  摘要：

  A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase (AChE) have been synthesized and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), and AChE-induced A beta aggregation. These compounds consist of a unit of tacrine or 6-chlorotacrine, which occupies the same position as tacrine at the AChE active site, and the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone moiety of donepezil (or the indane derivative thereof), whose position along the enzyme gorge and the peripheral site can be modulated by a suitable tether that connects tacrine and donepezil fragments. All of the new compounds are highly potent inhibitors of bovine and human AChE and BChE, exhibiting IC50 values in the subnanomolar or low nanomolar range in most cases. Moreover, six out of the eight hybrids of the series, particularly those bearing an indane moiety, exhibit a significant A beta antiaggregating activity, which makes them promising anti-Alzheimer drug candidates.

  DOI：

  10.1021/jm8001313
• 作为产物：
  描述：

  9-[(2-methanesulfonyloxyethyl)amino]-1,2,3,4-tetrahydroacridine 、 5,6-二甲氧基-2-(4-哌啶基)亚甲基-1-茚酮 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 以20%的产率得到9-[(2-{4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidin-1-yl}ethyl)amino]-1,2,3,4-tetrahydroacridine
  参考文献：
  名称：

  Novel Donepezil-Based Inhibitors of Acetyl- and Butyrylcholinesterase and Acetylcholinesterase-Induced β-Amyloid Aggregation

  摘要：

  A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase (AChE) have been synthesized and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), and AChE-induced A beta aggregation. These compounds consist of a unit of tacrine or 6-chlorotacrine, which occupies the same position as tacrine at the AChE active site, and the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone moiety of donepezil (or the indane derivative thereof), whose position along the enzyme gorge and the peripheral site can be modulated by a suitable tether that connects tacrine and donepezil fragments. All of the new compounds are highly potent inhibitors of bovine and human AChE and BChE, exhibiting IC50 values in the subnanomolar or low nanomolar range in most cases. Moreover, six out of the eight hybrids of the series, particularly those bearing an indane moiety, exhibit a significant A beta antiaggregating activity, which makes them promising anti-Alzheimer drug candidates.

  DOI：

  10.1021/jm8001313

文献信息

• Novel Donepezil-Based Inhibitors of Acetyl- and Butyrylcholinesterase and Acetylcholinesterase-Induced β-Amyloid Aggregation
  作者：Pelayo Camps、Xavier Formosa、Carles Galdeano、Tània Gómez、Diego Muñoz-Torrero、Michele Scarpellini、Elisabet Viayna、Albert Badia、M. Victòria Clos、Antoni Camins、Mercè Pallàs、Manuela Bartolini、Francesca Mancini、Vincenza Andrisano、Joan Estelrich、Mònica Lizondo、Axel Bidon-Chanal、F. Javier Luque

  DOI：10.1021/jm8001313

  日期：2008.6.1

  A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase (AChE) have been synthesized and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), and AChE-induced A beta aggregation. These compounds consist of a unit of tacrine or 6-chlorotacrine, which occupies the same position as tacrine at the AChE active site, and the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone moiety of donepezil (or the indane derivative thereof), whose position along the enzyme gorge and the peripheral site can be modulated by a suitable tether that connects tacrine and donepezil fragments. All of the new compounds are highly potent inhibitors of bovine and human AChE and BChE, exhibiting IC50 values in the subnanomolar or low nanomolar range in most cases. Moreover, six out of the eight hybrids of the series, particularly those bearing an indane moiety, exhibit a significant A beta antiaggregating activity, which makes them promising anti-Alzheimer drug candidates.