Design, synthesis, and biological evaluation of (E)- and (Z)-styryl-2-acetoxyphenyl sulfides and sulfones as cyclooxygenase-2 inhibitors

Bioorg Med Chem. 2005 Mar 1;13(5):1715-23. doi: 10.1016/j.bmc.2004.12.005.

Abstract

A new series of styryl acetoxyphenyl sulfides and sulfones possessing (E)- and (Z)-configurations were designed and prepared by stereospecific syntheses. All these compounds were evaluated for their ability to inhibit COX-2 enzyme in vitro. Structure-activity relationship studies on these compounds revealed that only sulfides with (Z)-configuration have potential COX-2 inhibitory activity. This inactivation of the enzyme is believed to be due to the selective covalent modification of COX-2 by the inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Sheep
  • Sulfides / chemical synthesis*
  • Sulfides / chemistry
  • Sulfides / pharmacology*
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry
  • Sulfones / pharmacology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Sulfides
  • Sulfones
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases