ACS Med Chem Lett. 2020 Jan 9;11(2):166-171. doi: 10.1021/acsmedchemlett.9b00550. eCollection 2020 Feb 13.
Discovery of a New Sulfonamide Hepatitis B Capsid Assembly Modulator.
Na HG1,2, Imran A1, Kim K1,2, Han HS1,2, Lee YJ1,2, Kim MJ3, Yun CS1, Jung YS1,2, Lee JY4, Han SB1,2.
Author information
1
Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 34114, Republic of Korea.
2
Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea.
3
AM Sciences, C-912, SK V1 GL Metrocity, 128, Beobwon-ro, Songpa-gu, Seoul, 05854, Republic of Korea.
4
Chemical Data-Driven Research Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Republic of Korea.
Abstract
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.