N-sulfonylanthranilic acid derivatives as allosteric inhibitors of dengue viral RNA-dependent RNA polymerase

J Med Chem. 2009 Dec 24;52(24):7934-7. doi: 10.1021/jm901044z.

Abstract

A novel class of compounds containing N-sulfonylanthranilic acid was found to specifically inhibit dengue viral polymerase. The structural requirements for inhibition and a preliminary structure-activity relationship are described. A UV cross-linking experiment was used to map the allosteric binding site of the compound on the viral polymerase.

MeSH terms

  • Binding Sites
  • Dengue Virus / chemistry
  • Dengue Virus / drug effects
  • Dengue Virus / enzymology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • RNA-Dependent RNA Polymerase / chemistry
  • Structure-Activity Relationship
  • Sulfinic Acids / chemical synthesis
  • Sulfinic Acids / chemistry
  • Sulfinic Acids / pharmacology
  • ortho-Aminobenzoates / chemical synthesis
  • ortho-Aminobenzoates / chemistry*
  • ortho-Aminobenzoates / pharmacology*

Substances

  • Enzyme Inhibitors
  • Sulfinic Acids
  • ortho-Aminobenzoates
  • RNA-Dependent RNA Polymerase