Comparison of the anti-influenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo

Bioorg Med Chem. 2005 Jun 2;13(12):4071-7. doi: 10.1016/j.bmc.2005.03.048. Epub 2005 Apr 25.

Abstract

Cyclopentane derivatives, designated as BCX-1812, BCX-1827, BCX-1898, and BCX-1923, were tested in parallel with oseltamivir carboxylate and zanamivir for the in vivo activity in mice infected with A/Turkey/Mas/76 X A/Beijing/32/92 (H6N2) influenza virus. The compounds were tested orally and intranasally at different dose levels. BCX-1812, BCX-1827, and BCX-1923 showed more than 50% protection at 1mg/kg/day dose level on oral treatment. The intranasal treatment was 100% effective even at 0.01 mg/kg/day for all four compounds. On comparison with oseltamivir carboxylate and zanamivir, these four cyclopentane derivatives have shown equal or better efficacies. The synthesis of two new compounds, BCX-1898 and BCX-1923, is also described.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / pharmacology
  • Acids, Carbocyclic
  • Administration, Intranasal
  • Administration, Oral
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Cyclopentanes / administration & dosage*
  • Cyclopentanes / chemical synthesis*
  • Cyclopentanes / pharmacology
  • Dose-Response Relationship, Drug
  • Guanidines
  • Mice
  • Orthomyxoviridae / drug effects*
  • Orthomyxoviridae Infections / drug therapy
  • Oseltamivir
  • Pyrans
  • Sialic Acids / pharmacology
  • Structure-Activity Relationship
  • Survival Rate
  • Treatment Outcome
  • Zanamivir

Substances

  • Acetamides
  • Acids, Carbocyclic
  • Antiviral Agents
  • Cyclopentanes
  • Guanidines
  • Pyrans
  • Sialic Acids
  • Oseltamivir
  • Zanamivir
  • peramivir