Hepatitis C NS5B polymerase inhibitors: 4,4-Dialkyl-1-hydroxy-3-oxo-3,4-dihydronaphthalene-3-yl benzothiadiazine derivatives

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3887-90. doi: 10.1016/j.bmcl.2008.06.043. Epub 2008 Jun 18.

Abstract

4,4-Dialkyl-1-hydroxy-3-oxo-3.4-dihydronaphthalene-3-yl benzothiadiazine derivatives were synthesized and evaluated as inhibitors of genotypes 1a and 1b HCV NS5B polymerase. A number of these compounds exhibited potent activity against genotypes 1a and 1b HCV polymerase in both enzymatic and cell culture activities. A representative compound also showed favorable pharmacokinetics in the rat.

MeSH terms

  • Administration, Oral
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacokinetics*
  • Area Under Curve
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacokinetics*
  • Genotype
  • Infusions, Intravenous
  • Inhibitory Concentration 50
  • Models, Chemical
  • Rats
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / genetics

Substances

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