Characterization of the two major CYP450 metabolites of ozonide (1,2,4-trioxolane) OZ277

Bioorg Med Chem Lett. 2008 Mar 1;18(5):1555-8. doi: 10.1016/j.bmcl.2008.01.087. Epub 2008 Jan 30.

Abstract

The antimalarial synthetic ozonide OZ277 (RBx11160) was hydroxylated by human liver microsomes at the distal bridgehead carbon atoms of the spiroadamantane substructure to form two carbinol metabolites devoid of antimalarial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemistry
  • Adamantane / metabolism
  • Antimalarials / chemistry
  • Antimalarials / metabolism
  • Cytochrome P-450 Enzyme System / metabolism*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / metabolism*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / metabolism*
  • Humans
  • Microsomes, Liver / metabolism
  • Molecular Structure
  • Peroxides / chemistry*
  • Peroxides / metabolism*
  • Spiro Compounds / chemistry*
  • Spiro Compounds / metabolism*

Substances

  • 1,2,4-trioxane
  • Antimalarials
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • OZ381
  • OZ397
  • Peroxides
  • Spiro Compounds
  • arterolane
  • Cytochrome P-450 Enzyme System
  • Adamantane