QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF 5-LIPOXYGENASE INHIBITORS - INHIBITORY POTENCY OF PYRIDAZINONE ANALOGS

Quantitative structure-activity relationships (QSAR) of 72 1-phenyltet rahydropyridazin-3(2H)-one (I)analogues are examined for the inhibitor y potency (IC50) Of 5-lipoxygenase in a broken cell. The potency is in creased by lipophilic substituents at the 3'- and 4-positions. Substit uents with positive F value at the 4'-position also increase the poten cy, while substituents at the 3'-position with a positive R value decr ease it. The potency also decreases as the size of the 2'- and/or 4'-s ubstituents increases. Thioketone analogues are about 5 times more pot ent than the corresponding carbonyl analogues.