title: Quantitative structure-activity relationships of 5-lipoxygenase inhibitors. Inhibitory potency of pyridazinone analogues.
abstract: Quantitative structure-activity relationships (QSAR) of 72 1-phenyltetrahydropyridazin-3(2H)-one (I) analogues are examined for the inhibitory potency (IC50) of 5-lipoxygenase in a broken cell. The potency is increased by lipophilic substituents at the 3'- and 4'-positions. Substituents with positive F value at the 4'-position also increase the potency, while substituents at the 3'-position with a positive R value decrease it. The potency also decreases as the size of the 2'- and/or 4'-substituents increases. Thioketone analogues are about 5 times more potent than the corresponding carbonyl analogues.
authors.affiliation: Pharmaceutical Product Division, Abbott Laboratories, Abbott Park, IL 60064.
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.forename: Y C
authors.initials: YC
authors.lastname: Martin
authors.forename: D W
authors.initials: DW
authors.lastname: Brooks
authors.forename: R D
authors.initials: RD
authors.lastname: Dyer
authors.forename: G W
authors.initials: GW
authors.lastname: Carter
mesh_terms: D000818:Animals; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011724:Pyridazines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D016859:Lipoxygenase Inhibitors; D011724:Pyridazines