Synthesis of 3,4-dihydro-4-oxothieno[2,3-d]pyrimidine-2-carboxylates, a new series of orally active antiallergy agents

Abstract

A series of novel 3,4-dihydro-4-oxothieno[2,3-d]pyrimidine-2-carboxylic acid derivatives has been prepared and tested for antiallergenic activity. Members of the series, including both carboxylic acid salts and esters, have been found to exhibit oral activity in the rat passive cutaneous anaphylaxis (PCA) test. Activity is optimized by H or CH3 substitution at the 5 position and lower alkyl groups at the 6 position. Ethyl 6-ethyl-3,4-dihydro-4-oxothieno-[2,3-d]pyrimidine-2-carboxylate and 3,4-dihydro-5-methyl-6-(2-methylpropyl)-4-oxothieno[2,3-d]pyrimidine-2-carboxylic acid dipotassium salt were the most potent of the esters and salts, respectively. Such compounds have been shown to have a duration of action of up to 4 h in the PCA test and to inhibit both histamine release from rat peritoneal mast cells in vitro and allergen-induced bronchospasm in the rat lung.