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• W3046115938 abstract "Bruton's tyrosine kinase (BTK) is a key component in the B-cell receptor signaling pathway and is consequently a target for in vivo imaging of B-cell malignancies as well as in multiple sclerosis (MS) with positron emission tomography (PET). A recent Phase 2b study with Sanofi's BTK inhibitor, Tolebrutinib (also known as [a.k.a.] SAR442168, PRN2246, or BTK'168) showed significantly reduced disease activity associated with MS. Herein, we report the radiosynthesis of [11 C]Tolebrutinib ([11 C]5) as a potential PET imaging agent for BTK. The N-[11 C]acrylamide moiety of [11 C]5 was labeled by 11 C-carbonylation starting from [11 C]CO, iodoethylene, and the secondary amine precursor via a novel palladium-NiXantphos-mediated carbonylation protocol, and the synthesis was fully automated using a commercial carbon-11 synthesis platform (TracerMaker™, Scansys Laboratorieteknik). [11 C]5 was obtained in a decay-corrected radiochemical yield of 37 ± 2% (n = 5, relative to starting [11 C]CO activity) in >99% radiochemical purity, with an average molar activity of 45 GBq/μmol (1200 mCi/μmol). We envision that this methodology will be generally applicable for the syntheses of labeled N-acrylamides." @default.
• W3046115938 created "2020-08-03" @default.
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• W3046115938 date "2020-08-13" @default.
• W3046115938 modified "2023-10-16" @default.
• W3046115938 title "Radiosynthesis of a Bruton's tyrosine kinase inhibitor, [ ¹¹ C]Tolebrutinib, via palladium‐NiXantphos‐mediated carbonylation" @default.
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• W3046115938 doi "https://doi.org/10.1002/jlcr.3872" @default.
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