3-(O)-glycinylgalantamine | 1197472-97-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: 3-(O)-glycinylgalantamine
• CAS: 1197472-97-1
• 化学式: C₁₉H₂₄N₂O₄
• 分子量: 344.411
• InChiKey: JCUZWARJMKHMCU-RFUYNDQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.36
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  74.02
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-(3-carbonyloxy-(1-methyl-6,7-dimethoxyquinolinium))pyrolidine-2,5-dione triflate 、 3-(O)-glycinylgalantamine 在 resin-supported N-benzyl-1,4-dihydronicotinamide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 4.5h， 生成 3-(O)-[(N-methyl-6,7-dimethoxydihydroquinolin-3-carboxamide)glycinyl]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
• 作为产物：
  描述：

  在 哌啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以88%的产率得到3-(O)-glycinylgalantamine
  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

文献信息

• Synthesis and biological study of new galanthamine-peptide derivatives designed for prevention and treatment of Alzheimer’s disease
  作者：Lyubomir T. Vezenkov、Dancho L. Danalev、Iwan Iwanov、Valentin Lozanov、Atanas Atanasov、Rumyana Todorova、Nikolay Vassilev、Veronika Karadjova

  DOI：10.1007/s00726-022-03167-z

  日期：2022.6

  The Alzheimer’s disease leads to neurodegenerative processes and affecting negatively million people worldwide. The treatment of the disease is still difficult and incomplete in practice. Galanthamine is one of the most commonly used drugs against the illness. The main aim of this work is design and synthesis of new derivatives of galanthamine comprising peptide moiety as well as study of their β-secretase

  阿尔茨海默病导致神经退行性过程，并对全世界数百万人产生负面影响。该病的治疗在实践中仍然困难且不完整。加兰他敏是最常用的治疗该疾病的药物之一。这项工作的主要目的是设计和合成包含肽部分的加兰他敏新衍生物，以及研究它们的β-分泌酶抑制活性和抗聚集作用。所有含有 Leu-Val-Phe-Phe (Aβ17-Aβ20) 类似物的加兰他敏新衍生物均使用片段和连续缩合方法在溶液中合成。通过熔点、NMR 和 HPLC/MS 对新衍生物进行了表征。通过荧光法在体外测试了它们的β-分泌酶抑制活性，并在体外研究了它们对绵羊富含血小板的血浆的抗聚集活性。尽管新化合物不含负责抑制 β-分泌酶的结构元素，但其中 5 种显示出高或良好的 β-分泌酶抑制活性，IC 值在 19.98% 和 51.19% 之间50在 1.95 和 5.26 nM 之间。其中四种新分子能够抑制 55.0 至 90.0% 的血小板聚集，IC 50为