Synthesis and anti-influenza activities of carboxyl alkoxyalkyl esters of 4-guanidino-Neu5Ac2en (zanamivir)

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.

Graphical abstractThe modified analogs of zanamivir carboxylic moiety with alkoxyalkyl esters 1a–c potentially inhibited influenza virus in cell culture and in mice.Figure optionsDownload full-size imageDownload as PowerPoint slide