4-hydroxythiazole inhibitors of 5-lipoxygenase.
4-Hydroxythiazoles have been identified as potent inhibitors of 5-lipoxygenase in vitro exhibiting IC50's of less than 1 microM. An investigation of structure-activity relationships showed that the most potent inhibitors of this series are the 5-phenyl derivatives. The corresponding thiazolidin-4-one analogues were found to be relatively inactive. The 4-hydroxythiazoles were active inhibitors against 5-lipoxygenase in both intact rat polymorphonuclear leukocytes and human whole blood. The compounds were also selective inhibitors of 5-lipoxygenase, displaying only weak activity against other related enzymes, cyclooxygenase and 12- and 15-lipoxygenase.
Kerdesky
F A
FA
Immunosciences Research Area, Abbott Laboratories, Abbott Park, Illinois 60064.
Holms
J H
JH
Moore
J L
JL
Bell
R L
RL
Dyer
R D
RD
Carter
G W
GW
Brooks
D W
DW
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood; D055598:Chemical Phenomena; D002621:Chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; D001094:Arachidonate 5-Lipoxygenase