Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
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DOI：
10.1021/jacs.7b03131
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发表时间：
2017-06-21
影响因子：
15
通讯作者：
Gouverneur, Veronique
中科院分区：
文献类型：
--
作者：
Taylor, Nicholas J.;Emer, Enrico;Gouverneur, Veronique
用氟-18(F-18)标记的分子用于正电子发射断层扫描，以可视化、表征和测量体内的生物过程。尽管最近在将F-18结合到芳烃上取得了进展，但开发通用和有效的方法来标记药物发现计划所需的放射性配体仍然是一项重要的任务。本文描述了一种以铜介导的芳基硼试剂与F-18-氟化物的F-18-氟化反应为模型反应合成杂环正电子发射断层扫描(PET)放射性配体的去风险方法。这一方法是基于一项研究，该研究考察了药物开发中常用的杂环的存在如何影响具有代表性的芳基硼试剂的F-18-氟化效率，以及对50多个(杂环)芳基硼酸酯的标记。这组数据允许将这一去风险策略应用于七个结构复杂的、与药物相关的杂环分子的成功放射合成。
Molecules labeled with fluorine-18 (F-18) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of F-18 onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated F-18-fluorination of aryl boron reagents with F-18-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of F-18-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally omplex pharmaceutically relevant heterocycle-containing molecules.