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

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3227-31. doi: 10.1016/j.bmcl.2011.04.052. Epub 2011 Apr 21.

Abstract

We describe the structure-activity relationship of the C7-position 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 compounds 13 and 14.

MeSH terms

  • Allosteric Site
  • Crystallography, X-Ray
  • Drug Discovery*
  • Enzyme Inhibitors* / chemical synthesis
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology*
  • Indoles* / chemical synthesis
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • Pyrans* / chemical synthesis
  • Pyrans* / chemistry
  • Pyrans* / pharmacology
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

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