Synthesis and in vitro evaluation of fluorine-18 benzimidazole sulfones as CB2 PET-radioligands

Annukka Kallinen, Rochelle Boyd, Samuel Lane, Rajiv Bhalla, Karine Mardon, Damion H. R. Stimson, Eryn L. Werry, Roger Fulton, Mark Connor, Michael Kassiou*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)


    Cannabinoid type 2 receptor (CB2) is up-regulated on activated microglial cells and can potentially be used as a biomarker for PET-imaging of neuroinflammation. In this study the synthesis and pharmacological evaluation of novel fluorinated pyridyl and ethyl sulfone analogues of 2-(tert-butyl)-5-((2-fluoropyridin-4-yl)sulfonyl)-1-(2-methylpentyl)-1H-benzo[d]imidazole (rac-1a) are described. In general, the ligands showed low nanomolar potency (CB2 EC50 < 10 nM) and excellent selectivity over the CB1 subtype (>10 000×). Selected ligands 1d, 1e, 1g and 3l showing high CB2 binding affinity (Ki < 10 nM) were radiolabelled with fluorine-18 from chloropyridyl and alkyl tosylate precursors with good to high isolated radioactive yields (25-44%, non-decay corrected, at the end of synthesis). CB2-specific binding of the radioligand candidates [18F]-1d and [18F]-3l was assessed on rat spleen cryosections using in vitro autoradiography. The results warrant further in vivo evaluation of the tracer candidates as prospective CB2 PET-imaging agents.

    Original languageEnglish
    Pages (from-to)5086-5098
    Number of pages13
    JournalOrganic and Biomolecular Chemistry
    Issue number20
    Publication statusPublished - 28 May 2019


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