Synthesis and antiviral/antitumor activities of certain pyrazolo[3,4-d]pyrimidine-4(5H)-selone nucleosides and related compounds.
Several pyrazolo[3,4-d]pyrimidine-4(5H)-selone ribonucleosides were prepared as potential antiparasitic agents. Treatment of 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine (5a) with selenourea and subsequent deacetylation gave 1-beta-D-ribofuranosylpyrazolo[3,4-d] pyrimidine-4(5H)-selone (6a). A similar treatment of 3-bromo-4-chloro-1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine (5b) with selenurea, followed by debenzoylation, gave the 3-bromo derivative of 6a (6b). Glycosylation of persilylated 4-chloro-6-methyl-pyrazolo [3,4-d]pyrimidine (7) with tetra-O-acetylribofuranose (8) provided the key intermediate 4-chloro-6-methyl-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl) pyrazolo[3,4-d]pyrimidine (9). Ammonolysis of 9 gave 4-amino-6-methyl-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidine (10), whereas treatment with sodium hydroxide gave 6-methylallopurinol ribonucleoside (11a). Reaction of 9 with either thiourea or selenourea, followed by deacetylation, provided 6-methylpyrazolo[3,4-d]pyrimidine-4(5H)-thione ribonucleoside (11c) and the corresponding seleno derivative (11d), respectively. The structural assignment of these nucleosides was made on the basis of spectral studies. These compounds were tested in vitro against certain viruses and tumor cells. All the compounds except 11c exhibited significant activity against HSV-2 in vitro, whereas 11c exhibited the most potent activity against measles and has a very low toxicity. Compounds 6a, 6b, and 11d were found to be potent inhibitors of growth of L1210 and P388 leukemia in vitro.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008459:Measles virus / Q000187:drug effects; D051379:Mice; D009705:Nucleosides / Q000138:chemical synthesis* / Q000633:toxicity; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects; D012643:Selenium; D018139:Simplexvirus / Q000187:drug effects; D010948:Viral Plaque Assay
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009705:Nucleosides; D012643:Selenium