Racemic and chiral sulfoxides as potential prodrugs of 4-pyrone COX-2 inhibitors

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3605-8. doi: 10.1016/j.bmcl.2006.03.101. Epub 2006 May 2.

Abstract

The preparation of the sulfoxide analogues 7, 8, and 9 and their enantiomerically pure forms is discussed as well as their ability to act as prodrugs of the potent and selective sulfone-containing COX-2 inhibitors 1, 2, and 3. Sulfoxide derivatives 7 and 9 were shown to be rapidly transformed in vivo into the corresponding sulfone derivatives 1 and 3, after oral administration to rats.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Cyclooxygenase 1 / drug effects
  • Cyclooxygenase 2 / drug effects*
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Drug Evaluation, Preclinical
  • Humans
  • Male
  • Models, Molecular
  • Molecular Structure
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Rats
  • Rats, Wistar
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis
  • Sulfones / chemistry
  • Sulfones / pharmacology*
  • Sulfoxides / chemical synthesis
  • Sulfoxides / chemistry
  • Sulfoxides / pharmacology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Prodrugs
  • Sulfones
  • Sulfoxides
  • Cyclooxygenase 1
  • Cyclooxygenase 2