The structure-activity relationship of the antimalarial ozonide arterolane (OZ277)

J Med Chem. 2010 Jan 14;53(1):481-91. doi: 10.1021/jm901473s.

Abstract

The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / adverse effects
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antimalarials / therapeutic use
  • Heterocyclic Compounds, 1-Ring / chemical synthesis
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Heterocyclic Compounds, 1-Ring / therapeutic use
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology
  • Mice
  • Molecular Conformation
  • Parasitic Sensitivity Tests
  • Peroxides / chemical synthesis
  • Peroxides / pharmacokinetics
  • Peroxides / pharmacology*
  • Peroxides / therapeutic use
  • Plasmodium falciparum / drug effects*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / pharmacokinetics
  • Spiro Compounds / pharmacology*
  • Spiro Compounds / therapeutic use
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Heterocyclic Compounds, 1-Ring
  • Peroxides
  • Spiro Compounds
  • arterolane