Structure-activity relationship of new anti-hepatitis C virus agents: heterobicycle-coumarin conjugates

J Med Chem. 2009 Mar 12;52(5):1486-90. doi: 10.1021/jm801240d.

Abstract

For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which inhibited HCV replication at an EC(50) of 6.8, 2.0, and 12 microM, respectively. The heteroatoms in bicycles and the substituent effect on coumarin played essential roles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Benzoxazoles / chemical synthesis
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Coumarins / chemical synthesis*
  • Coumarins / chemistry
  • Coumarins / pharmacology
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Heterocyclic Compounds, 2-Ring / chemical synthesis*
  • Heterocyclic Compounds, 2-Ring / chemistry
  • Heterocyclic Compounds, 2-Ring / pharmacology
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Models, Molecular
  • Purines / chemical synthesis
  • Purines / chemistry
  • Purines / pharmacology
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • RNA, Viral / drug effects
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Benzoxazoles
  • Coumarins
  • Heterocyclic Compounds, 2-Ring
  • Imidazoles
  • Purines
  • Pyridines
  • RNA, Viral