Na Hyo Gyeong, Imran Ali, Kim Kyuneun, Han Hong Sik, Lee Young Jin, Kim Myung-Jin, Yun Chang-Soo, Jung Young-Sik, Lee Joo-Youn, Han Soo Bong
Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 34114, Republic of Korea.
Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea.
ACS Med Chem Lett. 2020 Jan 9;11(2):166-171. doi: 10.1021/acsmedchemlett.9b00550. eCollection 2020 Feb 13.
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 , a potent CAM belonging to the SBA class. The lead compound () exhibited improved pharmacological activity and was examined through molecular docking studies.
乙型肝炎病毒（HBV）仍然是一个重大的健康问题，全球有2.6亿人受到感染，每年约有68万人死于肝硬化和肝癌。调节HBV衣壳组装已成为治疗慢性HBV感染的一种有前景的治疗方法。小分子衣壳组装调节剂（CAMs）大致可分为杂芳基二氢嘧啶和氨磺酰苯甲酰胺（SBAs）。SBAs是衣壳激活剂，通过在聚合酶封装之前实现衣壳组装来抑制病毒复制。在此，我们报告了一系列基于一种属于SBA类的强效CAM的新型HBV CAMs。先导化合物（）表现出改善的药理活性，并通过分子对接研究进行了考察。
