DEVELOPMENT OF ETHYL 3,4-DIHYDRO-4-OXOPYRIMIDO[4,5-B]QUINOLINE-2-CARBOXYLATE, A NEW PROTOTYPE WITH ORAL ANTIALLERGY ACTIVITY

Structural modification of 3.4-dihydro-4-oxoquinazoline-2-carboxvlic acid leading to ethyl 3, 4-dihydro-4-oxopyrimido[4, 5-b)]quinoline-2-carboxylate, a new prototype with oral antiallergv activity of the disodium cromoglycate type, is described. This prototype is 10 times more potent than disodium cromoglycate in the rat passive cutaneous anaphylaxis test. Structure activity studies indicate that a carboxvlic acid moiety directly attached to the 2 position of the pyrimidine ring is most favorable for intravenous activity while esters of this acid are preferred for oral activity. The oral activity of ethyl 3, 4-dihydro-4-oxopyrimido|4, 5-b]quinoline-2-carboxylate (ED50 = 3 mg/kg) places this ester among the more potent orally active antiallergv agents reported to date. © 1979, American Chemical Society. All rights reserved.