Abstract: AIMTo design and synthesize new derivatives of azithromycin, based on the distribution features of azithromycin in vivo and to improve the selectivity and activity of antiviral agents using the 15 membered-ring macrolide as the carrier. METHODSNew derivatives of azithromycin were designed on O₂ computer-aided workstation and synthesized through two paths, anti-HBV (hepatits B viral) reagent screening model was used to carry out pharmacological research. RESULTSThree new azithromycin derivatives and two intermediates were synthesized. Target compounds 4a, 4b and 5 are confirmed to be correct by spectrum analysis. Pharmacological results indicate that some of them showed antiviral activity. CONCLUSIONOne of the new azithromycin derivatives 4b showed anti-virus effect. The design method is correct, which may be used to instruct the design of similar compounds.