115891-11-7

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 sereis, 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(1H)-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.