The HBV capsid modulators derived from sulfamoylbenzamides and benzamides: an overview of the progress of patents

Hepatitis B virus (HBV) capsid assembly has become an attractive target for the therapy of chronic HBV infection. Since the first report of phenylpropenamides as effective capsid assembly modulators (CAMs) in 1998, dozens of structurally diversified CAMs have been disclosed in both scientific journals and patent publications. Herein, we present an overview of the patent applications derived from sulfamoylbenzamides (SBAs) and benzamides (BAs), two important classes of CAMs that have led to four human clinical phase 1 candidates, based on the publication dates, with their main Markush structures and molecular examples. This perspective will provide an overview of the recent advances that have appeared in patent applications, outline the new modulator designs and the evolution of chemical spaces from the initial SBA and BA leads, as well as demonstrate the efforts for new intellectual property (IP) positions. Graphical Abstract