Drug-induced modifications of the immune response. 12. 4,5-Dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids and derivatives as novel antiallergic agents

• Published in: Journal of medicinal chemistry Vol. 31; no. 10; pp. 1910 - 1918
• Main Authors: Mack, Robert A, Zazulak, Walter I, Radov, Lesley A, Baer, Jane E, Stewart, Jeffrey D, Elzer, Philip H, Kinsolving, C. Richard, Georgiev, Vassil S
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.10.1988
• Subjects: Animals; Antibody Formation - drug effects; Bradykinin - pharmacology; Capillary Permeability - drug effects; Furans - pharmacology; Histamine - pharmacology; Hypersensitivity - drug therapy; Rats; Serotonin - pharmacology; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00118a008

The synthesis of a series of novel 4,5-dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids, salts, esters, and amides is described. The title compounds when tested in the mediator-induced dermal vascular permeability and active anaphylaxis assays in rats demonstrated moderate to potent antiallergic activity. The [2-trans-(4-methylphenyl)cyclopropyl]amino analogue 53 emerged as the most active derivative. Thus, when administered intraperitoneally to rats at a dose of 100 mg/kg, it inhibited the action of the mediators serotonin, histamine, and bradykinin by 100%. In the active anaphylaxis assay in rats, compound 30 suppressed the edema by 81% at a dose of 100 mg/kg, following intraperitoneal administration.