SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 6-HYDROXYGUANIDINOPURINE AND 6-HYDROXYUREIDOPURINE AND THEIR RIBONUCLEOSIDES

N6-(1-hydroxyguanidino)purine IIa, and its 9-β-D-ribonucleoside derivative IIb were prepared by reacting at room temperature 6-hydroxyadenine Ia and 6-hydroxyadenosine lb, with 1-guanyl-3,5-dimethylpyrazole nitrate in DMF. Refluxing IIa and IIb in 95% ethanol gave N6-(1-hydroxyureido)purine and its ribonucleoside derivative respectively; the latter compound was also obtained by refluxing Ib with 1-guanyl-3,5-dimethylpyrazole nitrate in ethanol. The two base analogs were inactive against L1210 cells in vitro, but the nucleoside derivatives inhibited the growth of these cells by 50% at 5 x 10-6 and 6 x 10-7 M respectively. Compound lib, at 200 mg/kg/day x 5, increased the life span of L1210-bearing DBA/2N mice by 57%. Cytofluorometric determinations showed that. © 1990, Taylor & Francis Group, LLC. All rights reserved.