The metabolism of pyrazolo (3,4-d) pyrimidines by the rat.

The recent development of a new series of carcinostatic purine analogs, the pyrazolo(3,4-d)pyrimidines (5), has led to their study as substrates and inhibitors of certain purine oxidation systems in vitro (1,4). In the course of these studies, it was observed that purified xanthine oxidase incubated in vitro with 4-aminopyrazolo(3,4-d)pyrimidine (pyrazoloadenine) resulted in its oxidation to 4amino-6-hydroxypyrazolo(3,4-d)pyrimidine (pyrazoloisoguanine) (2). It seemed of interest to as certain whether this in vitro phenomenon repre sents an in vivo catabolic pathway of this drug. Knowledge of the catabolism of carcinostatic agents is both of intrinsic interest and of possible importance in gaining insight into tissue specifici ties and the development of resistance toward such compounds by tumors.