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

Area of Science:

• Hepatology
• Virology
• Medicinal Chemistry

Background:

• Hepatitis B Virus (HBV) infections pose a significant global health challenge.
• Current nucleoside analogue therapies for HBV have limited cure rates.
• Capsid assembly modulators (CAMs) show promise but face development hurdles.

Purpose of the Study:

• To optimize a lead series of HBV capsid assembly modulators (CAMs).
• To identify a preclinical candidate with improved potency, solubility, and reduced hERG liability.

Main Methods:

• Lead series optimization focusing on key drug-like properties.
• Iterative chemical modifications guided by structure-activity relationships.

Main Results:

• Successful optimization yielded AIC263282, a novel potent CAM.
• AIC263282 exhibits improved physicochemical properties compared to earlier compounds.
• The compound is suitable for further preclinical candidate profiling.

Conclusions:

• AIC263282 represents a promising advancement in HBV CAM development.
• This optimized molecule addresses critical limitations of previous CAMs.
• AIC263282 is a strong candidate for preclinical evaluation in HBV therapy.