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

Article abstract of DOI:10.1021/jm00191a009

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]pyridine-2-carboxylate and 3,4-dihydro-5-methyl-6-(2-methylpropyl)-4-oxothiene[2,3-d]pyridine-2-carboxylic acid potassium salt were the most potent bronchospasm 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 bronchoaspasm in the rat lung.