18F‐Radiopharmaceutical Diversification Enabled by Deaminative Cross‐Electrophile Couplings
Isabella F. Ogilvy, Joseph Ford, Sebastiano Ortalli, Evelien Renders, Thomas R. Hayes, Shuanglong Liu, Inne Mortiers, Anastasia Nikolopoulou, Alexandre M. Sorlin, Andrés A. Trabanco, Matthew Tredwell, Peter J. J. A. Buijnsters, Rhys Salter, Véronique Gouverneur
TL;DR
A new nickel-mediated chemical method enables efficient creation of 18F-labeled radiotracers for PET imaging and drug discovery.
Contribution
A nickel-mediated cross-coupling method for late-stage diversification of 18F-radiopharmaceuticals is introduced.
Findings
The method achieved up to 86% radiochemical conversion using amine-derived alkyl salts.
Six 18F-labeled GSK-3 kinase inhibitor analogues were produced in sufficient quantities for imaging.
The approach was successfully applied across three commercial radiosynthesis platforms.
Abstract
The development of 18F‐labelled radiotracers is of vital importance for (pre)clinical positron emission tomography (PET) imaging and to guide drug discovery campaigns. State‐of‐the‐art approaches often require labour‐intensive preparation of highly functionalised radiolabelling precursors. This bottleneck impedes analogue generation for optimal imaging and exploration of radiochemical space. To this end, we disclose a nickel‐mediated aryl (C)sp 2‐(C)sp 3 cross‐coupling with amine‐derived alkyl 2,4,6‐triphenylpyridinium salts as coupling partners amenable to radiosynthesis. The method was applied to primary and secondary 2,4,6‐triphenylpyridinium salts in radiochemical conversion (RCC) up to 86% and a high‐throughput experimentation (HTE) assay proved crucial for expedient ligand evaluation. A late‐stage diversification case study from a sole precursor achieved six 18F‐labelled GSK‐3…
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Taxonomy
TopicsRadiopharmaceutical Chemistry and Applications · Medical Imaging Techniques and Applications · Click Chemistry and Applications