title: Antiallergy agents. 1. Substituted 1,8-naphthyridin-2(1H)-ones as inhibitors of SRS-A release.
abstract: A novel class of antiallergy agents, the substituted 1,8-naphthyridin-2(1H)-ones, is described. The present compounds are orally active, potent inhibitors of allergic and nonallergic bronchospasm in animal models. Structure-activity studies of the lead compound in this series, 1-phenyl-3-n-butyl-4-hydroxynaphthyridin-2(1H)-one (11), identified three compounds of interest, 1-phenyl-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H)-one (12), 1-(3'-chlorophenyl)-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H )-one (87), and 1-(3'-methoxyphenyl)-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1 H)-one (89). The mechanism of antiallergy activity may involve inhibition of the release of the sulfidopeptide leukotrienes. 1-Phenyl-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H)-one, Sch 33303 (12), was selected for preclinical development as an antiallergy agent.
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D006634:Histamine H1 Antagonists; D009287:Naphthyridines; D013189:SRS-A; C057582:Sch 33303