Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities

► Thirty-five zanamivir analogs with C-4-modification were synthesized. ► Their inhibitory activities against neuraminidase (NA) (H5N1 and H3N2) were tested. ► Their anti-avian influenza virus (AIV, H5N1) activities were tested. ► Compound D26 showed good NA inhibition and D5 showed good anti-AIV efficacy. ► In silico docking studies were carried out to support the enzyme inhibition assay.