3-(O)-[6,7-dimethoxy-2-(3-tetrahydropyranyloxypropyl)quinolin-3-carbonyl]galantamine ester | 1616865-13-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 3-(O)-[6,7-dimethoxy-2-(3-tetrahydropyranyloxypropyl)quinolin-3-carbonyl]galantamine ester
• CAS: 1616865-13-4
• 化学式: C₃₇H₄₄N₂O₈
• 分子量: 644.765
• InChiKey: KMUYPFOIAIFYMV-DIUNUTQZSA-N

物化性质

• 熔点：
  82 °C
• 沸点：
  752.3±60.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.76
• 重原子数：
  47.0
• 可旋转键数：
  10.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  97.81
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  3-(O)-[6,7-dimethoxy-2-(3-tetrahydropyranyloxypropyl)quinolin-3-carbonyl]galantamine ester 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 以70%的产率得到3-(O)-[7,8-dimethoxypyrrolo[1,2a]quinolinium-3-carbonyl]galantamine ester bromide
  参考文献：
  名称：

  New developments in redox chemical delivery systems by means of 1,4-dihydroquinoline-based targetor: Application to galantamine delivery to the brain

  摘要：

  The therapeutic efficiency of palliative treatments of AD, mostly based on acetylcholinesterase (AChE) inhibitors, is marred by serious adverse effects due to peripheral activity of these AChE inhibitors. In the literature, a redox-based chemical delivery system (CDS) has been developed to enhance drugs distribution to the brain while reducing peripheral side effects. Herein, we disclose two new synthetic strategies for the preparation of 1,4-dihydroquinoline/quinolinium salt redox-based systems particularly well designed for brain delivery of drugs sensitive to alkylation reactions. These strategies have been applied in the present case to the AChE inhibitor galantamine with the aim of alleviating adverse effects observed with cholinergic AD treatment. The first strategy is based on an intramolecular alkylation reaction as key step, whilst the second strategy relies on a useful coupling between galantamine and quinolinium salt key intermediate. In the course of this work, polymer-supported reagents and a solid-phase synthesis approach revealed to be highly helpful to develop this redox-based galantamine CDS. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.022
• 作为产物：
  描述：

  ethyl 2-(3-hydroxypropyl)-6,7-dimethoxyquinoline-3-carboxylate 在 4-二甲氨基吡啶 、 4-甲基苯磺酸吡啶 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 40.0h， 生成 3-(O)-[6,7-dimethoxy-2-(3-tetrahydropyranyloxypropyl)quinolin-3-carbonyl]galantamine ester
  参考文献：
  名称：

  New developments in redox chemical delivery systems by means of 1,4-dihydroquinoline-based targetor: Application to galantamine delivery to the brain

  摘要：

  The therapeutic efficiency of palliative treatments of AD, mostly based on acetylcholinesterase (AChE) inhibitors, is marred by serious adverse effects due to peripheral activity of these AChE inhibitors. In the literature, a redox-based chemical delivery system (CDS) has been developed to enhance drugs distribution to the brain while reducing peripheral side effects. Herein, we disclose two new synthetic strategies for the preparation of 1,4-dihydroquinoline/quinolinium salt redox-based systems particularly well designed for brain delivery of drugs sensitive to alkylation reactions. These strategies have been applied in the present case to the AChE inhibitor galantamine with the aim of alleviating adverse effects observed with cholinergic AD treatment. The first strategy is based on an intramolecular alkylation reaction as key step, whilst the second strategy relies on a useful coupling between galantamine and quinolinium salt key intermediate. In the course of this work, polymer-supported reagents and a solid-phase synthesis approach revealed to be highly helpful to develop this redox-based galantamine CDS. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.022