Disruption of the HBV capsid assembly process through small-molecule interaction with HBV core protein is a validated target for the suppression of hepatitis B viral replication and the development of new antivirals. Through combination of key structural features associated with two distinct series of capsid assembly modulators, a novel aminochroman-based chemotype was identified. Optimization of anti-HBV potency through generation of SAR in addition to further core modifications provided a series of related functionalized aminoindanes. Key compounds demonstrated excellent cellular potency in addition to favorable ADME and pharmacokinetic profiles and were shown to be highly efficacious in a mouse model of HBV replication. Aminoindane derivative AB-506 was subsequently advanced into clinical development.

通过与 HBV 核心蛋白的小分子相互作用破坏 HBV 衣壳组装过程是抑制乙型肝炎病毒复制和开发新型抗病毒药物的有效靶标。通过与两个不同系列的衣壳组装调节剂相关的关键结构特征的组合，鉴定出一种新的基于氨基色满的化学型。通过生成 SAR 以及进一步的核心修饰来优化抗 HBV 效力，提供了一系列相关的功能化氨基茚满。除了良好的 ADME 和药代动力学特征外，关键化合物还表现出优异的细胞效力，并且在 HBV 复制的小鼠模型中显示出高度有效。氨基茚满衍生物AB-506随后进入临床开发。