Non-nucleoside inhibitors of the hepatitis C virus NS5B RNA-dependant RNA polymerase: 2-aryl-3-heteroaryl-1,3-thiazolidin-4-one derivatives

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6110-4. doi: 10.1016/j.bmcl.2008.10.023. Epub 2008 Oct 8.

Abstract

Hepatitis C virus (HCV) NS5B RNA polymerase is crucial for replicating the HCV RNA genome and is an attractive target for developing anti-HCV drugs. A novel series of 2,3-diaryl-1,3-thiazolidin-4-one derivatives were evaluated for their ability to inhibit HCV NS5B. Of this series, compounds 4c, 5b, 5c and 6 emerged as more potent, displaying over 95% inhibition of NS5B RNA polymerase activity in vitro. The two most active compounds 4c and 5c exhibited an IC(50) of 31.9 microM and 32.2 microM, respectively, against HCV NS5B.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Hepacivirus / drug effects*
  • Hepatitis C / drug therapy
  • Inhibitory Concentration 50
  • Molecular Structure
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Thiazolidines
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase