Pyrazole-Related Nucleosides. Synthesis and Antiviral/Antitumor Activity of Some Substituted Pyrazole and Pyrazolo-1,2,3-triazin-4-one Nucleosides

Article abstract of DOI:10.1021/jm00083a017

Several pyrazole and pyrazolo<4,3-d>-1,2,3-triazin-4-one ribonucleosides were prepared and tested for antiviral/antitumor activities.Appropriate heterocyclic bases were prepared by standard methodologies.Glycosylation of pyrazoles 6a-e,g,i and pyrazolo<4,3-d>-1,2,3-triazin-4-ones 12f-l mediated bu silylation with hexamethylsilazane, with 1-β-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose gave in good yields the corresponding glycosides 7a-e,g, 8g,i 13f,h,k, and 14f, but could not be applied to compounds 12g,i,j,l.To overcome this occurrence, a different strategy involvi ng the preparation, diazotization, and in situ cyclization of opportune pyrazole glycosides 9 and 10 was reguired.Moreover derivatives having the general formula 5 were considered not only as synthetic intermediates in the synthesis of 3 but also as carbon bioisosteres of ribavirin 4.All compounds were evaluated in vitro for cytostatic and antiviral activity.The pyrazolo<4,3-d>-1,2,3-triazin-4-one nucleosides that resulted were substantially devoid of any activity; only 15h,k showed a moderate cytostatic activity against T-cells.However, pyrazole nucleosides 9b,c,e were potent and selective cytotoxic agents against T-lymphocytes, whereas 9e showed a selective, although not very potent, activity against coxsackie B1.