MCR 支架通过 F 标记变得更热。

MCR Scaffolds Get Hotter with F-Labeling.

机构信息

Department of Drug Design, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.

Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

出版信息

Molecules. 2019 Apr 4;24(7):1327. doi: 10.3390/molecules24071327.

Imaging techniques, such as positron emission tomography (PET), represent great progress in the clinical development of drugs and diagnostics. However, the efficient and timely synthesis of appropriately labeled compounds is a largely unsolved problem. Numerous small drug-like molecules with high structural diversity can be synthesized via convergent multicomponent reactions (MCRs). The combination of PET labeling with MCR synthesis of biologically active compounds can greatly simplify radioanalytical and imaging-based analysis. In a proof-of-concept study, we optimized robust on-site radiolabeling conditions that were subsequently applied to several structurally different drug-like MCR scaffolds (e.g., arenes, β-lactam, tetrazole, and oxazole). These labeled scaffolds were synthesized via pinacol-derived aryl boronic esters (arylBPin) by copper-mediated oxidative F-fluorination with radiochemical conversions (RCCs) from 15% to 76%.

成像技术，如正电子发射断层扫描（PET），代表了药物和诊断学临床发展的重大进展。然而，高效、及时地合成适当标记的化合物是一个尚未解决的大问题。通过收敛型多组分反应（MCR）可以合成具有高结构多样性的许多小型类似药物的分子。将 PET 标记与生物活性化合物的 MCR 合成相结合，可以大大简化基于放射分析和成像的分析。在一项概念验证研究中，我们优化了稳健的现场放射性标记条件，随后将其应用于几种结构不同的类似药物的 MCR 支架（如芳烃、β-内酰胺、四唑和恶唑）。这些标记的支架是通过 pinacol 衍生的芳基硼酸酯（arylBPin）通过铜介导的氧化 F-氟化作用合成的，放射性化学转化率（RCC）为 15%至 76%。