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Parallel synthesis of 5-cyano-6-aryl-2-thiouracil derivatives as inhibitors for hepatitis C viral NS5B RNA-dependent RNA polymerase.

Abstract
From random screening of our compound libraries, we identified a hit compound with an IC50 of 27 microM against hepatitis C viral NS5B RNA-dependent RNA polymerase. By using a parallel synthetic strategy, a series of its derivatives were synthesized. From their anti-HCV activity screening, compounds with single digital 3.8 micromolar activity were obtained.
AuthorsYili Ding, Jean-Luc Girardet, Kenneth L Smith, Gary Larson, Brett Prigaro, Jim Z Wu, Nanhua Yao
JournalBioorganic chemistry (Bioorg Chem) Vol. 34 Issue 1 Pg. 26-38 (Feb 2006) ISSN: 0045-2068 [Print] United States
PMID16360193 (Publication Type: Journal Article)
Chemical References
  • 2-Pyridin-2-yl-1H-indole
  • Antiviral Agents
  • Enzyme Inhibitors
  • Indoles
  • Pyridines
  • Viral Nonstructural Proteins
  • 5-cyanouracil
  • Uracil
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase
Topics
  • Antiviral Agents (chemical synthesis, pharmacology)
  • Enzyme Inhibitors (chemical synthesis, pharmacology)
  • Hepacivirus (drug effects, enzymology)
  • Humans
  • Indoles (chemical synthesis, metabolism)
  • Inhibitory Concentration 50
  • Pyridines (chemical synthesis, metabolism)
  • RNA-Dependent RNA Polymerase (antagonists & inhibitors, metabolism)
  • Structure-Activity Relationship
  • Uracil (analogs & derivatives, chemical synthesis, pharmacology)
  • Viral Nonstructural Proteins (genetics, metabolism)
  • Virus Replication (drug effects)

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