Synthesis of 1,4-triazole linked zanamivir dimers as highly potent inhibitors of influenza A and B†
Benjamin H. Fraser,Stephanie Hamilton,Anwen M. Krause-Heuer,Philip J. Wright,Ivan Greguric,Simon P. Tucker,Alistair G. Draffan,Valery V. Fokin,K. Barry Sharpless
Abstract
The copper catalyzed azide alkyne cycloaddition (CuAAC) reaction – the quintessential ‘click’ reaction – was used to synthesise dimers of the neuraminidase inhibitor zanamivir in high yields. The effect upon anti-viral activity of varying the linker length and the number of triazole units was explored. All dimers were tested for anti-viral activity against influenza A/Sydney/5/97 and B/Harbin/7/94 in a cytopathic effect (CPE) assay.
