Discovery of thiophene-2-carboxylic acids as potent inhibitors of HCV NS5B polymerase and HCV subgenomic RNA replication. Part 1: Sulfonamides

Bioorg Med Chem Lett. 2004 Feb 9;14(3):793-6. doi: 10.1016/j.bmcl.2003.10.067.

Abstract

The discovery of a novel class of HCV NS5B polymerase inhibitors, 3-arylsulfonylamino-5-phenyl-thiophene-2-carboxylic acids is described. SAR studies have yielded several potent inhibitors of HCV polymerase as well as of HCV subgenomic RNA replication in Huh-7 cells.

MeSH terms

  • Carboxylic Acids
  • Carcinoma, Hepatocellular / chemistry
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / virology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Genome, Viral
  • Hepacivirus / enzymology*
  • Humans
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / virology
  • RNA, Viral / metabolism*
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • Replicon / drug effects
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Virus Replication / drug effects

Substances

  • Carboxylic Acids
  • Enzyme Inhibitors
  • RNA, Viral
  • Sulfonamides
  • Thiophenes
  • Viral Nonstructural Proteins
  • 2-thiophene carboxylic acid
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase