Analogs of arachidonic acid methylated at C-7 and C-10 as inhibitors of leukotriene biosynthesis

The syntheses and biological activity of (all Z )-7,7-dimethyl-5-8,- 11,14-eicosatetraenoic acid, (all Z )-7,7,-dimethyl-5,8,11-eicosatrienoic acid, ( Z , Z -7,7-dimethyl-5,8-eicosadienoic acid, (all Z )-10,10-dimetyl- 5,8,11,14-eicosatetraenoic acid, (all Z -10,10-dimethyl-5,8,11-eicosatrienoic acid, and rac .-( Z , Z -15-hydroxy-7,7-dimethyl-5,8-eicosadienoic acid are described. These arachidonic acid analogs are all inhibitors of ionophore-induced SRS-A biosynthesis in rat peritoneal cells. Their mode of action may involve inhibition of phospholipase A2 rather than Δ5-lipoxygenase. These compounds failed to exhibit significant activity in an in vivo model designed to detect inhibitors of antigen-induced, leukotriene-mediated bronchoconstriction is sensitized guinea pigs.