R. Wayne Rundles, M.D., F.A.C.P.; Harold R. Silberman, M.D., F.A.C.P.; George H. Hitchings, Ph.D.; Gertrude B. Elion, Ph.D.
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A series of pyrazolopyrimidines synthesized some years ago as potential purine antagonists were found to be active in suppressing the growth of bacteria, fungi, tumor cells in culture, and rodent neoplasms. Some of the purine isomers were effective inhibitors of xanthine oxidase in vitro. Two of the most promising compounds, 4-amino- and 4-propylaminopyrazolo (3,4-d)-pyrimidines, were studied clinically as anticancer agents. Their predominant effect was hepatic toxicity.
We have found more recently that a major loss in activity of 6-MP and derivatives in man results from oxidative degradation. The possibility of circumventing this by the administration of 4-hydroxypyrazolo (3,4-d)-pyrimidine (HPP), a
Rundles RW, Silberman HR, Hitchings GH, Elion GB. Effects of Xanthine Oxidase Inhibitor on Clinical Manifestations and Purine Metabolism in Gout.. Ann Intern Med. ;60:717–718. doi: 10.7326/0003-4819-60-4-717_2
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Published: Ann Intern Med. 1964;60(4):717-718.
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