Synthesis and biological evaluation of xanthine oxidase inhibitors. Pyrazolo(3,4-d)pyrimidines and pyrazolo(3,4-b)pyridines.

1-, 3-, and 5-substituted pyrazolo[3,4-d]pyrimidines and pyrazolo[3,4-b]pyridines related to allopurinol were synthesized and evaluated as xanthine oxidase inhibitors. Among these compounds, 4-hydroxypyrazolo[3,4-b]pyridine-5-carboxylic acids 12 were found to possess potency in the same order of allopurinol. The influence of the substitutions on the enzyme inhibitory effect and the bulk tolerance of the enzyme-inhibitor complex are discussed.