Pyrazolopyrimidine nucleosides. 12. Synthesis and biological activity of certain pyrazolo[3,4-d]pyrimidine nucleosides related to adenosine.
The chemical synthesis of certain 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides is described. Using 1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (1) as the starting material, the reactive intermediate 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (2) was prepared in excellent yield. Compound 2 served as a versatile precursor for the synthesis of a number of 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides. In antitumor studies of these nucleosides, in vitro and in vivo, it was found that any alteration of the 4-amino substituent of 4-amino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidine (3) was accompanied by a significant decrease or loss of antitumor activity. On the other hand, introduction of certain substituents at the 3 position of 3 (synthesis reported previously) led to a dramatic increase in antitumor activity in comparison to the parent compound.
D000241:Adenosine / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D009705:Nucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D011720:Pyrazoles / Q000138:chemical synthesis / Q000627:therapeutic use; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009705:Nucleosides; D011720:Pyrazoles; D011741:Pyrimidine Nucleosides; D000241:Adenosine