Syntheses of triazole-modified zanamivir analogues via click chemistry and anti-AIV activities

Sixteen novel 4-triazole-modified zanamivir (1) analogues were synthesized using the click reactions, and their inhibitory activities against avian influenza virus (AIV, H5N1) were determined. Compound 3b exerts promising inhibitory activity with EC50 of 6.4 μM, which is very close to that of zanamivir (EC50 = 2.8 μM). Molecular modeling provided the information about the binding model between inhibitors and neuraminidase, which are in good agreement with inhibitory activities.