title: 4-hydroxythiazole inhibitors of 5-lipoxygenase.
abstract: 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.
authors.affiliation: Immunosciences Research Area, Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: F A
authors.initials: FA
authors.lastname: Kerdesky
authors.forename: J H
authors.initials: JH
authors.lastname: Holms
authors.forename: J L
authors.initials: JL
authors.lastname: Moore
authors.forename: R L
authors.initials: RL
authors.lastname: Bell
authors.forename: R D
authors.initials: RD
authors.lastname: Dyer
authors.forename: G W
authors.initials: GW
authors.lastname: Carter
authors.forename: D W
authors.initials: DW
authors.lastname: Brooks
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; D001094:Arachidonate 5-Lipoxygenase