(±)-9-[(3-chloro-6,7,10,11-tetrahydro-9-methyl-7,11-methanocycloocta[b]quinolin-12-yl)amino]nonanenitrile

• 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-[(3-chloro-6,7,10,11-tetrahydro-9-methyl-7,11-methanocycloocta[b]quinolin-12-yl)amino]nonanenitrile
• 英文别名: 9-[[(1S,13S)-7-chloro-15-methyl-10-azatetracyclo[11.3.1.02,11.04,9]heptadeca-2,4(9),5,7,10,14-hexaen-3-yl]amino]nonanenitrile
• 化学式: C₂₆H₃₂ClN₃
• 分子量: 422.013
• InChiKey: BLPYTBKGSNFTAZ-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (±)-9-[(3-chloro-6,7,10,11-tetrahydro-9-methyl-7,11-methanocycloocta[b]quinolin-12-yl)amino]nonanenitrile 在 氯甲酸乙酯 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 75.5h， 生成 9-[(3-chloro-6,7,10,11-tetrahydro-9-methyl-7,11-methanocycloocta[b]quinolin-12-yl)amino]-N-(4-hydroxy-3-methoxybenzyl)nonanamide
  参考文献：
  名称：

  Discovery of a Potent Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase with Antioxidant Activity that Alleviates Alzheimer-like Pathology in Old APP/PS1 Mice

  摘要：

  DOI：

  10.1021/acs.jmedchem.0c01775
• 作为产物：
  描述：

  7-chloro-15-methyl-10-azatetracyclo[11.3.1.0^2,11.0^4,9]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine hydrochloride 、 9-bromononanenitrile 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以66%的产率得到(±)-9-[(3-chloro-6,7,10,11-tetrahydro-9-methyl-7,11-methanocycloocta[b]quinolin-12-yl)amino]nonanenitrile
  参考文献：
  名称：

  Synthesis and Multitarget Biological Profiling of a Novel Family of Rhein Derivatives As Disease-Modifying Anti-Alzheimer Agents

  摘要：

  We have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer's disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase, butyrylcholinesterase, and BACE-1, dual Aβ42 and tau antiaggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction, preventing the loss of synaptic proteins and/or have a positive effect on the induction of long-term potentiation. In vivo studies in APP-PS1 transgenic mice treated ip for 4 weeks with (+)- and (-)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.

  DOI：

  10.1021/jm401824w

文献信息

• Beta-Amyloid-Directed Multitarget Compounds For The Treatment Of Alzheimer's Disease
  申请人：UNIVERSITAT DE BARCELONA

  公开号：US20150099776A1

  公开（公告）日：2015-04-09

  The compounds of formula (I), or its pharmaceutically acceptable salts, or any stereoisomer or mixture thereof, wherein: R 1 is a (C 1 -C 2 ) alkyl radical; R 2 and R 3 are radicals independently selected from the group consisting of F, Cl and methyl R 4 is H or OH; A is a birradical selected from the group consisting of —(CH 2 ) n — and —(CH 2 )-phenyl-(CH 2 )—; t is an integer from 0 to 1; and n is an integer from 8 to 15, are useful for the treatment of Alzheimer's disease.
• US9238626B2
  申请人：——

  公开号：US9238626B2

  公开（公告）日：2016-01-19
• Discovery of a Potent Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase with Antioxidant Activity that Alleviates Alzheimer-like Pathology in Old APP/PS1 Mice
  作者：Elisabet Viayna、Nicolas Coquelle、Monika Cieslikiewicz-Bouet、Pedro Cisternas、Carolina A. Oliva、Elena Sánchez-López、Miren Ettcheto、Manuela Bartolini、Angela De Simone、Mattia Ricchini、Marisa Rendina、Mégane Pons、Omidreza Firuzi、Belén Pérez、Luciano Saso、Vincenza Andrisano、Florian Nachon、Xavier Brazzolotto、Maria Luisa García、Antoni Camins、Israel Silman、Ludovic Jean、Nibaldo C. Inestrosa、Jacques-Philippe Colletier、Pierre-Yves Renard、Diego Muñoz-Torrero

  DOI：10.1021/acs.jmedchem.0c01775

  日期：2021.1.14
• Synthesis and Multitarget Biological Profiling of a Novel Family of Rhein Derivatives As Disease-Modifying Anti-Alzheimer Agents
  作者：Elisabet Viayna、Irene Sola、Manuela Bartolini、Angela De Simone、Cheril Tapia-Rojas、Felipe G. Serrano、Raimon Sabaté、Jordi Juárez-Jiménez、Belén Pérez、F. Javier Luque、Vincenza Andrisano、M. Victòria Clos、Nibaldo C. Inestrosa、Diego Muñoz-Torrero

  DOI：10.1021/jm401824w

  日期：2014.3.27

  We have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer's disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase, butyrylcholinesterase, and BACE-1, dual Aβ42 and tau antiaggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction, preventing the loss of synaptic proteins and/or have a positive effect on the induction of long-term potentiation. In vivo studies in APP-PS1 transgenic mice treated ip for 4 weeks with (+)- and (-)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.