Synthesis and Evaluation of N-Phenyl-3-sulfamoyl-benzamide Derivatives as Capsid Assembly Modulators Inhibiting Hepatitis B Virus (HBV)

J Med Chem. 2018 Jul 26;61(14):6247-6260. doi: 10.1021/acs.jmedchem.8b00654. Epub 2018 Jul 3.

Abstract

Small molecule induced hepatitis B virus (HBV) capsid assembly modulation is considered an attractive approach for new antiviral therapies against HBV. Here we describe efforts toward the discovery of a HBV capsid assembly modulator in a hit-to-lead optimization, resulting in JNJ-632, a tool compound used to further profile the mode of action. Administration of JNJ-632 (54) in HBV genotype D infected chimeric mice resulted in a 2.77 log reduction of the HBV DNA viral load.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / metabolism
  • Benzamides / pharmacology*
  • Capsid / drug effects*
  • Capsid / metabolism
  • Chemistry Techniques, Synthetic
  • Genotype
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / metabolism*
  • Hepatitis B virus / physiology
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Protein Conformation
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / metabolism
  • Sulfonamides / pharmacology*
  • Viral Load / drug effects

Substances

  • Antiviral Agents
  • Benzamides
  • JNJ-632
  • Sulfonamides