Discovery of a New Sulfonamide Hepatitis B Capsid Assembly Modulator
Discovery of a New Sulfonamide Hepatitis B Capsid Assembly Modulator
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DOI：
10.1021/acsmedchemlett.9b00550
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发表时间：
2020-02-01
影响因子：
4.2
通讯作者：
Han, Soo Bong
中科院分区：
文献类型：
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作者：
Na, Hyo Gyeong;Imran, Ali;Han, Soo Bong
B型肝炎病毒（HBV）仍然是一个主要的健康问题，全球有2.6亿人受到感染，每年约有680，000人死于肝硬化和肝癌。HBV衣壳组装的调节已经成为治疗慢性HBV感染的有希望的治疗方法。小分子衣壳组装调节剂（CAM）可以广泛地分类为杂芳基二氢嘧啶和氨磺酰基苯甲酰胺（SBA）。SBA是衣壳活化剂，其通过在聚合酶包封之前实现衣壳组装来抑制病毒复制。在此，我们报告了一系列新的HBV CAM的基础上NVR 3-778，一个有效的CAM属于SBA类。先导化合物（KR-26556）表现出改善的药理活性，并通过分子对接研究进行了检查。
Hepatitis B virus (HBV) remains a major health concern with 260 million people having been infected globally, and approximately 680,000 deaths have occurred annually from cirrhosis and liver cancer. The modulation of HBV capsid assembly has emerged as a promising therapeutic approach for curing chronic HBV infection. Small-molecule capsid assembly modulators (CAMs) can broadly be classified as heteroaryldihydropyrimidines and sulfamoylbenzamides (SBAs). SBAs are capsid activators that inhibit viral replication by achieving capsid assembly before polymerase encapsulation. Herein, we report a novel series of HBV CAMs based on NVR 3-778, a potent CAM belonging to the SBA class. The lead compound (KR-26556) exhibited improved pharmacological activity and was examined through molecular docking studies.