Synthesis and Biological Evaluation of Entecavir 4'-Ester Derivatives

Entecavir can significantly inhibit the replication of HBV-DNA, reduce the HBV-DNA level in blood serum. But suffering from low oral bioavailability, entecavir has low intestinal membrane permeability and poor metabolic stability. In this study, 12 different derivatives of entecavir 4'-ester were regioselectively synthesized and their apical-to-basolateral permeabilities across Caco-2 cells and HBV-DNA inhibitory efficacies were evaluated. Most of the compounds showed high permeabilities across Caco-2 cells compared with entecavir, compounds 5b and 5e also exhibited comparable anti-HBV activities with that of entecavir, especially.