Discovery of 5‐alkyl‐2‐pyrazol‐oxazolidin‐4‐one derivatives as novel hepatitis B virus capsid assembly modulators

Abstract

AbstractThe “magic methyl effect” strategy was used to design a series of 5‐alkyl‐2‐pyrazol‐oxazolidin‐4‐one derivatives as novel hepatitis B virus (HBV) capsid assembly modulators. Most of these compounds exhibited potent HBV inhibitory activities with low cytotoxicities in HepG2.2.15 cells. The most promising compounds 9d and 10b had single‐digit nanomolar IC50 values with a high selectivity index. Compared with the lead compound (3.0%), they caused 15% and 18% decreases in HBe antigen secretion at 1.0 μM, respectively. In addition, compounds 9d and 10b possessed good pharmacokinetic profiles with oral bioavailability values of 56.1% and 48.9%, respectively. These results indicated that the two compounds were potential therapeutic agents for HBV infection.