Synthesis and biological activity of heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone derivatives as hepatitis C virus NS5B polymerase inhibitors

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4354-8. doi: 10.1016/j.bmcl.2009.05.080. Epub 2009 May 27.

Abstract

Modification of the benzo rings of 3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones into heteroaromatic systems was investigated to enhance physicochemical properties and potency profile of this class of inhibitors. The synthesis and biological activity of the derived compounds is discussed.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Genotype
  • Hepacivirus / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Structure
  • Protein Binding
  • Quinolones / chemical synthesis*
  • Quinolones / pharmacology
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Quinolones
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus