Synthesis and biological evaluation of 1,3-diphenylprop-2-yn-1-ones as dual inhibitors of cyclooxygenases and lipoxygenases

Bioorg Med Chem Lett. 2005 Nov 1;15(21):4842-5. doi: 10.1016/j.bmcl.2005.07.036.

Abstract

A new class of 1,3-diphenylprop-2-yn-1-ones possessing a p-MeSO2 COX-2 phamacophore on the C-3 phenyl ring was designed for evaluation as dual inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX). Among the group of compounds evaluated, 1-(4-fluorophenyl)-3-(4-methanesulfonylphenyl)prop-2-yn-1-one (11j) exhibited excellent COX-2 inhibitory potency (COX-2 IC50 = 0.1 microM) and selectivity (SI = 300), whereas 1-(4-cyanophenyl)-3-(4-methanesulfonylphenyl)prop-2-yn-1-one (11d) exhibited an optimal combination of COX and LOX inhibition (COX-2 IC50 = 1.0 microM; COX-2 SI = 31.5; 5-LOX IC50 = 1.0 microM; 15-LOX IC50 = 3.2 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemical synthesis
  • Alkynes / pharmacology
  • Animals
  • Binding Sites
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / pharmacology
  • Glycine max
  • Inhibitory Concentration 50
  • Ketones / chemical synthesis
  • Ketones / pharmacology
  • Lipoxygenase Inhibitors / chemical synthesis*
  • Lipoxygenase Inhibitors / pharmacology
  • Mice
  • Models, Molecular
  • Sheep
  • Solanum tuberosum
  • Structure-Activity Relationship

Substances

  • Alkynes
  • Cyclooxygenase Inhibitors
  • Ketones
  • Lipoxygenase Inhibitors
  • methylacetylene