Nicky Hwang, Shuo Wu, Haiqun Ban, Huixin Luo, Julia Ma, Junjun Cheng, Qiong Zhao, Jessilyn A Laney, Na Du, Junyang Guo, Manasa Suresh, Liangxian Shen, Gideon Tolufashe, Usha Viswanathan, John Kulp, Patrick Lam, Jinhong Chang, Jason A Clement, Stephan Menne, Ju-Tao Guo, Yanming Du
A key step of hepatitis B virus (HBV) replication is the selective packaging of pregenomic RNA (pgRNA) by core protein (Cp) dimers, forming a nucleocapsid where the reverse transcriptional viral DNA replication takes place. One approach in the development of new anti-HBV drugs is to disrupt the assembly of HBV nucleocapsids by misdirecting Cp dimers to assemble morphologically normal capsids devoid of pgRNA. In this study, we built upon our previous discovery of benzamide-derived HBV capsid assembly modulators by exploring fused bicyclic scaffolds with an exocyclic amide that is β, γ to the fused ring, and identified 1,2,3,4-tetrahydroquinoxaline derived phenyl ureas as a novel scaffold...
July 17, 2023: European Journal of Medicinal Chemistry