SYNTHESIS AND BIOLOGICAL-ACTIVITY OF THE NOVEL ADENOSINE-ANALOGS - NO-6-(BETA-D-RIBOFURANOSYL)PYRAZOLO[3,4-C]PYRAZOLE AND YL-6-(BETA-D-RIBOFURANOSYL)PYRAZOLO[3,4-C]PYRAZOLE

Chemical modification of the 4-nitrile group in enzyl-beta-D-ribofuran osyl)pyrazole-4-carbonitrile (1) afforded -(2,3,5-tri-O-benzyl-beta-D- ribofuranosyl)pyrazole (3). The methylation of 3, via a three step pro cedure, gave -(2,3,5-tri-O-benzyl-beta-D-ribofuranosyl)pyrazole (3a). The mononuclear heterocyclic rearrangement (m.h.r) of 3 and 3a, provid ed a convenient route to the novel azapentalene adenosine analogs no-6 -(beta-D-ribofuranosyl)pyrazolo3,4-cpyrazole (6) and 3-amino-1-methy l-6-(beta-D-ribofuranosyl)pyrazolo 3,4-cpyrazole (6a), respectively. Compound 6 exhibited no cytotoxicity when screened in vitro against e ither mouse L1210 leukemic cells or human foreskin fibroblasts. Nor wa s it active against human cytomegalovirus. Compound 6a was designed an d prepared to investigate the possibility that the lack of biological activity of 6 might be due to annular tautomerization limiting the abi lity of 6 to serve as a substrate for the activating enzyme adenosine kinase. This hypothesis was neither supported nor disproved by the res ults, as compound 6a was also inactive in both the antiproliferative a nd antiviral test systems.