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Enabling SF5 introduction: Paving the way toward unexplored bioisosteres and novel PET radiotracers

Organofluorine scaffolds hold an increasingly privileged position as drug candidates, diagnostic PET radiotracers and agrochemicals. In fact, about half of the novel FDA-approved small molecules in 2018 contained a fluorinated moiety. Recent development of a plethora of bench-stable transfer reagents for fluorinated functionalities has substantially expanded the arsenal of fluorine-containing molecules at our disposal. Despite these advances, a bench-stable reagent capable of transferring the pentafluorosulfanyl (-SF5) group, is still lacking from the toolbox, even though this functional group is commonly considered a “super-CF3“ group on account of its excellent pharmacological properties. Still less accessible are scaffolds of the type -SF4R, which nevertheless represent an entire gamut of under-explored bioisosteric replacements. Herein, we propose a strategy that entails the development of SF5-donating reagents, and their valorisation in user-friendly synthetic approaches toward pentafluorosulfanylated molecules. Second, we aim to access first-in-class [18F]SF5-containing radiotracers for PET imaging studies, via late-stage [18F]-labeling. Third, we will target the general preparation of a wide variety of -SF4R type groups, and gain insight on their biological properties. Overall, the proposal spans chemical tool development in both organic synthesis and radiochemistry, focusing on the construction of novel scaffolds containing the pentafluorosulfanyl group.
Date:1 Oct 2020 →  31 Dec 2020
Keywords:pentafluorosulfanyl, bench-stable reagent, fluorine, [18F]-radiolabeling, bioisosterism, PET imaging
Disciplines:Organic chemical synthesis, Nuclear chemistry, Medicinal chemistry