2-pyridylimidazoles as inhibitors of xanthine oxidase

A series of 28 4-substituted and 4,5-disubstituted 2-pyridylimidazoles was synthesized and evaluated in vitro for inhibition of xanthine oxidase. Included within this group are examples of 2-pyridylimidazopyridines and halo-substituted 2-pyridylbenzimidazoles. Five compounds exhibited inhibitory activity in the same range as the standards, 4-hydroxypyrazolo[3,4-d]pyrimidine and 2-(4-pyridyl)-4-trifluoromethylimidazole (22). Two examples, 2-(4-pyridyl)-4,5-dicyanoimidazole (16) and 2-(4-pyridyl)-4-nitroimidazole (3), were at least an order of magnitude more active than the standards and therefore rank among the most potent known inhibitors of the enzyme.