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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 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.