title: Synthesis and antiallergic activity of a novel series of 5-lipoxygenase inhibitors.
abstract: A series of novel substituted [[(phenoxymethyl)phenyl]amino]oxoalkanoic acid esters have been synthesized. These compounds were tested in vitro for their ability to inhibit the synthesis of 5-hydroxyeicosatetraenoic acid and leukotriene (LT) B4 from rat polymorphonuclear leukocytes (PMN) and in vivo as inhibitors ovalbumin- (OA) and LTD4-induced bronchospasm in the guinea pig. Compounds 5-12 and 25 had IC50's between 1 and 5.6 microM in the rat PMN 5-lipoxygenase assay. Compounds 1, 3, and 16 inhibited OA-induced bronchoconstriction (61%, 64%, and 57%, respectively), but only 1 showed activity against LTD4-induced bronchoconstriction. When tested against LTD4-induced contraction of isolated guinea pig tracheal spiral strips, 1 was a competitive inhibitor with a pKB of 4.94.
mesh_terms: D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D001980:Bronchi / Q000187:drug effects; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006967:Hypersensitivity / Q000188:drug therapy*; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D013189:SRS-A / Q000037:antagonists & inhibitors
chemical_list: D006634:Histamine H1 Antagonists; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D001091:Arachidonate Lipoxygenases