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-dimethyl-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 delta 5-lipoxygenase. These compounds failed to exhibit significant activity in an in vivo model designed to detect inhibitors of antigen-induced, leukotriene-mediated bronchoconstriction in sensitized guinea pigs.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D006168:Guinea Pigs; D008745:Methylation; D013189:SRS-A / Q000096:biosynthesis*
D001095:Arachidonic Acids; D013189:SRS-A; D000001:Calcimycin