Development of ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate, a new prototype with oral antiallergy...

Structural modification of 3,4-dihydro-4-oxoquinazoline-2-carboxylic acid leading to ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate, a new prototype with oral antiallergy 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 carboxylic 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 antiallergy agents reported to date.