Discovery of AIC263282, a Hepatitis B Virus Capsid Assembly Modulator Ready for Candidate Profiling

Hepatitis B Virus (HBV) infections remain a threat to the global public health. Nucleoside analogues remain the mainstay of therapy despite their discouraging cure rates achieved. Capsid assembly modulators (CAMs) have been at the center of HBV research, but despite having shown clinical efficacy on viral load in clinical studies, market entry has been elusive. Herein, we present the optimization program of our lead series. Setting our focus on potency, solubility, and hERG liability, these studies resulted in AIC263282, a new, potent capsid assembly modulator with improved physicochemical properties, which is ready for profiling as a preclinical candidate.