Antiallergy agents. 1. Substituted 1,8-naphthyridin-2(1H)-ones as inhibitors of SRS-A release

• Published in: Journal of medicinal chemistry Vol. 31; no. 11; pp. 2108 - 2121
• Main Authors: Sherlock, Margaret H, Kaminski, James J, Tom, Wing C, Lee, Joe F, Wong, Shing Chun, Kreutner, William, Bryant, Robert W, McPhail, Andrew T
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.11.1988
• Subjects: Animals; Asthma - metabolism; Asthma - physiopathology; Guinea Pigs; Histamine H1 Antagonists - pharmacology; Lung - metabolism; Naphthyridines - pharmacology; SRS-A - metabolism; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00119a010

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.