Synthesis and Structure-Activity Relationship Studies of Capsid Assembly Modulators Targeting Hepatitis B Virus

Abstract

Hepatitis B is difficult to be cured completely and is facing many difficulties in developing treatments. Currently using antiviral treatments can only inhibit the proliferation of viruses if it is taken continuously or have serious immune side effects. In this situation, Capsid Assembly Modulators (CAMs)are emerging as a new antiviral agent. Unlike other drugs, the CAM inhibits the core protein of the virus, preventing capsid formation and ultimately acting as this mechanism to prevent virus proliferation. Previous studies have reported that it has strong antiviral effects as CAMs and some compounds entered into clinical trials. Based on those studies, pyrimidine and pyridine core derivatives were synthesized and their inhibitory effects to viral DNA were evaluated through in vitro screening. At in vitro screening, compounds 18c showed inhibitory EC50 value at 0.085 μM and 30f approximately at 1 μM, especially 30f showed low toxicity and high bioavailability at oral administration.