Efficient synthesis of 3H,3′H-spiro[benzofuran-2,1′-isobenzofuran]-3,3′-dione as novel skeletons specifically for influenza virus type B inhibition

An efficient and novel two step synthetic procedure to prepare various substituted 3H,3′H-spiro[benzofuran-2,1′-isobenzofuran]-3,3′-diones A, was established from very simple and easily available starting materials. The developed method is a robust and general approach for the synthesis of these structures. The prepared compounds were tested against influenza virus type A viz., A/Taiwan/1/86 (H1N1), A/Hong Kong/8/68 (H3N2) and type B viz., B/Panama/45/90, B/Taiwan/2/62, B/Lee/40, B/Brisbane/60/2008. Among 31 compounds tested, some of them showed good activity (selective index values >10) against these influenza viruses preferentially for type B. The most active compound 3b showed activity in 3.0–16.1 μM range with a selectivity index value between 30 and 166 against these type B viruses, in which it was comparable to the antiviral agent favipiravir. Also, 3b is found to be inactive against other enveloped viruses (viz., HIV and HSV) showing its specificity for influenza viruses.

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► Efficient synthesis of 3H,3′H-spiro[benzofuran-2,1′-isobenzofuran]-3,3′-diones.
► Antiviral activity evaluation against different strains of Influenza Virus type B.
► Compound 3b shows better than known anti-influenza agent ribavarin.