ml9b00550_si_001.pdf (2.12 MB)
Discovery of a New Sulfonamide Hepatitis B Capsid Assembly Modulator
journal contribution
posted on 2020-01-15, 15:04 authored by Hyo Gyeong Na, Ali Imran, Kyuneun Kim, Hong Sik Han, Young Jin Lee, Myung-Jin Kim, Chang-Soo Yun, Young-Sik Jung, Joo-Youn Lee, Soo Bong HanHepatitis 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.