Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector

Eur J Med Chem. 2017 Sep 29;138:407-421. doi: 10.1016/j.ejmech.2017.06.062. Epub 2017 Jun 29.


The synthesis of novel series of sulfamoylbenzamides as HBV capsid assembly effector is reported. The structure was divided into five parts which were independently modified as part of our lead optimization. All synthesized compounds were evaluated for their anti-HBV activity and toxicity in human hepatocytes, lymphocytes and other cells. Additionally, we assessed their effect on HBV cccDNA formation in an HBeAg reporter cell-based assay. Among the 27 compounds reported, several analogs exhibited submicromolar activities and significant reduction of HBeAg secretion. Selected compounds were studied under negative-stain electron microscopy for their ability to disrupt the HBV capsid formation. Structures were modeled into a binding site recently identified in the HBV capsid protein for similar molecules to rationalize the structure-activity relationships for this family of compounds.

Keywords: Antiviral agent; Capsid assembly effector; HBV; HBeAg; Sulfamoylbenzamide; cccDNA.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Capsid / metabolism*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Hepatitis B virus / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Vero Cells
  • Virus Assembly / drug effects*


  • Antiviral Agents
  • Benzamides