Styrylpyrazoles, Styrylisoxazoles, and Styrylisothiazoles. Novel 5-lipoxygenase and Cyclooxygenase Inhibitors

J Med Chem. 1991 Feb;34(2):518-25. doi: 10.1021/jm00106a006.

Abstract

A series of styrylpyrazoles, styrylisoxazoles, and styrylisothiazoles were prepared and found to be dual inhibitors of 5-lipoxygenase and cyclooxygenase in rat basophilic leukemia cells. Compounds from this series also were found to inhibit the in vivo production of LTB4 when dosed orally in rats. Among these compounds, di-tert-butylphenols 19 and 33 exhibit oral activity in various models of inflammation and, most importantly, are devoid of ulcerogenic potential.

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Cyclooxygenase Inhibitors*
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / pharmacology
  • Leukotriene B4 / biosynthesis
  • Lipoxygenase Inhibitors*
  • Male
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology

Substances

  • Cyclooxygenase Inhibitors
  • Isoxazoles
  • Lipoxygenase Inhibitors
  • Pyrazoles
  • Thiazoles
  • Leukotriene B4