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.
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.
Mack
R A
RA
Department of Organic Chemistry, Pennwalt Corporation, Rochester, New York 14623.
Zazulak
W I
WI
Radov
L A
LA
Baer
J E
JE
Stewart
J D
JD
Elzer
P H
PH
Kinsolving
C R
CR
Georgiev
V S
VS
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
D005663:Furans; D012701:Serotonin; D006632:Histamine; D001920:Bradykinin