Styrylpyrazoles, styrylisoxazoles, and styrylisothiazoles. Novel 5-lipoxygenase and cyclooxygenase inhibitors.
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.
Flynn
D L
DL
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Belliotti
T R
TR
Boctor
A M
AM
Connor
D T
DT
Kostlan
C R
CR
Nies
D E
DE
Ortwine
D F
DF
Schrier
D J
DJ
Sircar
J C
JC
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008297:Male; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013844:Thiazoles; D007975:Leukotriene B4