2,5-dioxopyrrolidin-1-yl 6,7-dimethoxyquinoline-3-carboxylate | 1616865-15-6

• 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: 2,5-dioxopyrrolidin-1-yl 6,7-dimethoxyquinoline-3-carboxylate
• 英文别名: N-(3-carbonyloxy-6,7-dimethoxyquinoline)pyrrolidine-2,5-dione
• CAS: 1616865-15-6
• 化学式: C₁₆H₁₄N₂O₆
• 分子量: 330.297
• InChiKey: MPFYGABDWRCFHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.47
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  95.03
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidin-1-yl 6,7-dimethoxyquinoline-3-carboxylate 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 27.0h， 生成 3-((((2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methoxy)carbonyl)-6,7-dimethoxy-1-methylquinolin-1-ium trifluoromethanesulfonate
  参考文献：
  名称：

  Delivering FLT to the Central Nervous System by Means of a Promising Targeting System: Synthesis, [¹¹C]Radiosynthesis, and in Vivo Evaluation

  摘要：

  The development of delivery systems to transport some specific radiotracers across the blood-brain barrier (BBB) needs to be investigated for brain imaging. [F-18]FLT (3'-deoxy-3'-F-18-fluoro-L-thymidine), an analogue substrate of the nucleoside thymidine, has been developed as a proliferation tracer for oncological PET studies. Unfortunately, low-grade brain tumors are poorly visualized due to the low uptake of [18F]FLT in brain tissue, preventing its use in PET imaging to detect brain tumors at an early stage. Based on our previous work, a redox chemical delivery system (CDS) related to Bodor's strategy was developed to enable the penetration of FLT into the brain. To this end, FLT was covalently linked to a series of lipophilic carriers based on a 1,4-dihydroquinoline structure. To determine the best carrier, various sets of [C-11]CDS-FLT were prepared and injected into rats. Pleasingly, in vivo results let us suggest that this CDS is a promising approach to overcome the BBB to target low-grade brain tumors for PET imaging.

  DOI：

  10.1021/acschemneuro.7b00218
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 6,7-dimethoxyquinoline-3-carboxylic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以64%的产率得到2,5-dioxopyrrolidin-1-yl 6,7-dimethoxyquinoline-3-carboxylate
  参考文献：
  名称：

  Delivering FLT to the Central Nervous System by Means of a Promising Targeting System: Synthesis, [¹¹C]Radiosynthesis, and in Vivo Evaluation

  摘要：

  The development of delivery systems to transport some specific radiotracers across the blood-brain barrier (BBB) needs to be investigated for brain imaging. [F-18]FLT (3'-deoxy-3'-F-18-fluoro-L-thymidine), an analogue substrate of the nucleoside thymidine, has been developed as a proliferation tracer for oncological PET studies. Unfortunately, low-grade brain tumors are poorly visualized due to the low uptake of [18F]FLT in brain tissue, preventing its use in PET imaging to detect brain tumors at an early stage. Based on our previous work, a redox chemical delivery system (CDS) related to Bodor's strategy was developed to enable the penetration of FLT into the brain. To this end, FLT was covalently linked to a series of lipophilic carriers based on a 1,4-dihydroquinoline structure. To determine the best carrier, various sets of [C-11]CDS-FLT were prepared and injected into rats. Pleasingly, in vivo results let us suggest that this CDS is a promising approach to overcome the BBB to target low-grade brain tumors for PET imaging.

  DOI：

  10.1021/acschemneuro.7b00218

文献信息

• New developments in redox chemical delivery systems by means of 1,4-dihydroquinoline-based targetor: Application to galantamine delivery to the brain
  作者：Mihaela-Liliana Ţînţaş、Lénaïg Foucout、Sylvain Petit、Sylvain Oudeyer、Fabienne Gourand、Louisa Barré、Cyril Papamicaël、Vincent Levacher

  DOI：10.1016/j.ejmech.2014.05.022

  日期：2014.6

  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.