Aryl uracil inhibitors of hepatitis C virus NS5B polymerase: synthesis and characterization of analogs with a fused 5,6-bicyclic ring motif

Bioorg Med Chem Lett. 2013 Jun 15;23(12):3487-90. doi: 10.1016/j.bmcl.2013.04.057. Epub 2013 May 1.

Abstract

The synthesis and structure-activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon cell culture potencies in the low nanomolar range along with excellent rat pharmacokinetic values.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / chemistry*
  • Bridged Bicyclo Compounds / pharmacokinetics
  • Bridged Bicyclo Compounds / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Hepacivirus / enzymology
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • RNA-Dependent RNA Polymerase / metabolism
  • Rats
  • Structure-Activity Relationship
  • Uracil / antagonists & inhibitors*
  • Uracil / pharmacology
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Bridged Bicyclo Compounds
  • Enzyme Inhibitors
  • Viral Nonstructural Proteins
  • Uracil
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase