Studies on Antianaphylactic Agents. 7. Synthesis of Antiallergic 5-Oxo-5H-[1]benzopyrano[2,3-b]pyridines

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Abstract
5-Oxo-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylic acids and their tetrazole analogs were synthesized from 4-oxo-4H-1-benzopyran-3-carbonitriles or 2-amino-4-oxo-4H-1-benzopyran-3-carboxaldehydes. When administered i.v., they exhibited antiallergic activity in a reaginic PCA [passive cutaneous anaphylaxis]tests in rats. In the carboxylic acid series, the activity was influenced by the substituents at the 2-position and increased substantially in the following order: Me [methyl], OMe < NH2 < OH, H < NHOMe. In the tetrazole series, 2-unsubstituted derivatives showed the highest activity. Regardless of the kinds of substituents at positions 2 and 3, compounds bearing an alkyl group, especially an isopropyl group at the 7-position, were superior in activity to the corresponding unsubstituted compounds. Among these alkyl derivatives, 3-carboxylic acid deirvatives, i.e., (7-ethyl), 23 g (2-amino-7-isopropyl), [2-(methoxyamino)-7-isopropyl] and a 3-tetrazole derivative (7-isopropyl), were 41-184 times as potent as disodium cromoglycate. They also exhibited remarkable activity when administered orally; clinical studies on 23 g (AA-673) are in progress.