Synthesis and antiallergic activities of 1,3-oxazolo[4,5-h]quinolines.
A series of new 1,3-oxazolo[4,5-h]quinolines has been prepared. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (PCA). After several modifications of the original lead, the most potent compound of the series was determined to be 5-chloro-1,3-oxazolo[4,5-h]quinoline-2-carboxylic acid methyl ester (4a). It has an IC50 of 0.3 microM in the RMC assay and an ED50 (intraperitoneal) of 0.1 mg/kg in the PCA test, which is 10 times and 60 times more potent than disodium cromoglycate (DSCG), respectively. Of greater importance, it is orally active (ED50 = 0.5 mg/kg) as an inhibitor of the PCA test.
Musser
J H
JH
Jones
H
H
Sciortino
S
S
Bailey
K
K
Coutts
S M
SM
Khandwala
A
A
Sonnino-Goldman
P
P
Leibowitz
M
M
Wolf
P
P
Neiss
E S
ES
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004205:Cromolyn Sodium / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D010080:Oxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D010080:Oxazoles; D011804:Quinolines; D007073:Immunoglobulin E; C046483:quazolast; D004205:Cromolyn Sodium