Abstract
Twenty-five substituted 5-arylazopyrimidine derivatives have been prepared as potential "small molecule" antagonists of folic acid <i>via</i> reaction of 5-unsubstituted pyrim-idines with appropriate diazotized aniline derivatives. The antineoplastic activity of 19 of these compounds has been examined <i>in vivo</i> by means of a primary screening program utilizing five transplantable mouse tumors. At nontoxic dosages, several of these agents showed effective tumor growth inhibition, as evidenced by reduction in mean tumor size. Histopathological examination of mice treated with 2,4-diamino-6-hydroxy-5-phenylazopyrimidine revealed intestinal irritation and evidence of nephrotoxicity, as well as incomplete absorption of the drug.
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