Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors

Aleksandrs Pustenko, Alessio Nocentini, Anastasija Balašova, Ahmed Alafeefy, Mikhail Krasavin, Raivis Žalubovskis, Claudiu T. Supuran

    Research output

    4 Citations (Scopus)


    A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance.

    Original languageEnglish
    Pages (from-to)245-254
    JournalJournal of Enzyme Inhibition and Medicinal Chemistry
    Issue number1
    Early online date2 Dec 2019
    Publication statusPublished - 1 Jan 2020

    Scopus subject areas

    • Pharmacology
    • Drug Discovery

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