Synthesis and biological evaluation of dihydrofuran-fused perhydrophenanthrenes as a new anti-influenza agent having novel structural characteristic

Bioorg Med Chem. 2007 Jan 1;15(1):424-32. doi: 10.1016/j.bmc.2006.09.046. Epub 2006 Oct 10.

Abstract

Dihydrofuran-fused perhydrophenanthrenes were synthesized by means of o-quinodimethane chemistry with high generality and stereoselectivity, and found to exhibit potent anti-influenza activity. These compounds exerted an inhibitory effect on various strains of influenza virus growth, including influenza A and B, with a concentration dependent manner, and direct cytotoxicity was low. Several biological experiments suggested that these new drugs affected a virus replication process before mRNA synthesis stage. Novel rigid cage-type of structural characteristic of the compounds has not been found in hitherto anti-influenza drugs, and will provide new basis and motif for exploring promising and unprecedented anti-influenza agents.

MeSH terms

  • Animals
  • Antiviral Agents* / chemical synthesis
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Design
  • Furans / chemistry*
  • Influenza A virus / drug effects*
  • Influenza A virus / growth & development
  • Influenza B virus / drug effects*
  • Influenza B virus / growth & development
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Phenanthrenes / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Furans
  • Phenanthrenes