Structure-Activity Relationships in a Series of Novel 3,4-Dihydro-4-oxopyrimidoquinoline-2-carboxylic Acid Antiallergy Agents

Article abstract of DOI:10.1021/jm00177a010

A series of more than 50 new 3,4-dihydro-4-oxopyrimido<4,5-b>quinoline-2-carboxylic acid derivatives and related compounds with substituent variations at the 2, 3, and 5-9 positions was prepared and evaluated for antiallergy activity using the rat PCA assay.These compounds were obtained by the condensation of the appropriately substituted 2-aminoquinoline-3-carboxamides with dialkyl oxalates, followed by further chemical transformations.More than two-thirds of the compounds prepared exhibited intravenous activity ranging from 1 to 400 times disodium cromoglycate (DSCG).Structure-activity data suggest that the presence of a carboxylic acid moiety at the 2 position affords optimal potency and that esters are preferred for good oral absorption.Best oral activity, with ED₅₀ values ranging from 0.3 to 3.0 mg/kg, was displayed by ethyl esters with methoxy and/or ethoxy groups at the 7 and 8 positions.