Three alkoxyalkyl 2-carboxylate ester derivatives related to zanamivir were synthesized. All of the analogs of zanamivir modified at carboxylic moiety with alkoxyalkyl esters 1a-c showed higher activities than ribavirin on influenza A and B virus in the MDCK cells. Oral treatment or intraperitoneal administration of compound 1c showed significantly protective effects in mice infected with influenza A virus with low toxicities.