title: 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.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, Pennwalt Corporation, Rochester, New York 14623.
authors.forename: R A
authors.initials: RA
authors.lastname: Mack
authors.forename: W I
authors.initials: WI
authors.lastname: Zazulak
authors.forename: L A
authors.initials: LA
authors.lastname: Radov
authors.forename: J E
authors.initials: JE
authors.lastname: Baer
authors.forename: J D
authors.initials: JD
authors.lastname: Stewart
authors.forename: P H
authors.initials: PH
authors.lastname: Elzer
authors.forename: C R
authors.initials: CR
authors.lastname: Kinsolving
authors.forename: V S
authors.initials: VS
authors.lastname: Georgiev
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D005663:Furans / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006967:Hypersensitivity / Q000188:drug therapy*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; D012701:Serotonin; D006632:Histamine; D001920:Bradykinin