Quantitative Structure-Activity Relationships of 5-Lipoxygenase Inhibitors. Inhibitory Potency of Pyridazinone Analogues

Quantitative structure-activity relationships (QSAR) of 72 1-phenyttetrahydropyridazin-3(2H)-one (I) analogues are examined for the inhibitory potency (IC S0 ) of 5-lipoxygenase in a broken cell. The potency is increased by lipophilic substituents at the 3’- and 4’-positions. Substituents with positive 7 value at the 4’-position also increase the potency, while substituents at the 3’-position with a positive C 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.