Design, synthesis and anti-HBV activity of novel bis(trifluoroethyl)phosphonomethyl ether derivatives of acyclovir

A series of novel bis(trifluoroethyl)phosphonomethyl ether derivatives of acyclovir was synthesized and their in vitro anti-HBV activity was evaluated in HepG2 2.2.15 cells. In contrast to acyclovir, most of the described phosphonates emerged as potent inhibitors of HBV replication. Especially, the most active compound 11 with IC50 value of 2.92 μmol/L was 33 times more potent than acyclovir with IC50 value of 100 μmol/L.