The discovery and structure-activity relationships of pyrano[3,4-b]indole based inhibitors of hepatitis C virus NS5B polymerase

Bioorg Med Chem Lett. 2010 May 1;20(9):2968-73. doi: 10.1016/j.bmcl.2010.03.002. Epub 2010 Mar 6.

Abstract

We describe the structure-activity relationship of the C1-group of pyrano[3,4-b]indole based inhibitors of HCV NS5B polymerase. Further exploration of the allosteric binding site led to the discovery of the significantly more potent compound 12.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Discovery
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Pyrans / chemical synthesis
  • Pyrans / chemistry*
  • Pyrans / pharmacology
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism

Substances

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