Abstract：
Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, the hit compound CDI (IC50 = 2.46 ± 0.33 μM) was identified by screening of an in-house compound library. And then novel potent benzimidazole derivatives were designed and synthesized as core assembly modulators, and their antiviral effects were evaluated in vitro and in vivo biological experiments. The results indicated that compound 26f displayed the most optimized modulator of HBV capsid assembly (IC50 = 0.51 ± 0.20 μM, EC50 = 2.24 ± 0.43 μM, CC50 = 84.29 μM) and high selectivity index. Moreover, treatment with compound 26f for 14 days significantly decreased serum levels of HBV DNA levels in the Hydrodynamic-Injection (HDI) mouse model. Therefore, compound 26f could be considered as a promising candidate drug for further development of novel HBV CAMs with the desired potency and safety.
摘要：
乙型肝炎病毒（HBV）衣壳组装调节剂（CAM）代表了治疗HBV感染的有希望的治疗方法。在这项研究中,通过筛选内部化合物文库鉴定命中的化合物CDI(IC50=2.46±0.33μM)。然后设计并合成了新型有效的苯并咪唑衍生物作为核心组装调节剂，并在体外和体内生物学实验中评估了它们的抗病毒作用。结果表明，化合物26f显示出HBV衣壳组装的最优化调节剂（IC50=0.51±0.20μM，EC50=2.24±0.43μM，CC50=84.29μM)和高选择性指数。此外，在流体动力学注射(HDI)小鼠模型中,用化合物26f治疗14天显著降低血清HBVDNA水平。因此,化合物26f可以被认为是进一步开发具有所需效力和安全性的新型HBVCAM的有希望的候选药物。
