138786-93-3Relevant articles and documents
A New Direct Glycosylation of Pyrimidine, Pyrazole, Imidazole and Purine Heterocycles via their N-tetrahydropyranyl (THP) Derivatives
Manfredini, Stefano,Baraldi, Pier Giovanni,Bazzanini, Rita,Guarneri, Mario,Simoni, Daniele
, p. 583 - 584 (1994)
Pyrimidine, pyrazole, imidazole and purine N-tetrahydropyranyl (THP) derivatives have been converted in one-pot and in a regio- and stereo-selective manner into the corresponding β-D-2',3',5'-tri-O-benzoyl ribofuranosyl nucleoside derivatives on treatment with 1-β-acetyl-2',3',5'-tri-O-benzoyl-ribofuranose, hexamethyldisilazane (HMDS), trimethylsilyl chloride (TMSCl), and trimethylsilyl triflate (TMST).
Effects of introduction of hydrophobic group on ribavirin base on mutation induction and anti-RNA viral activity
Moriyama, Kei,Suzuki, Tetsuya,Negishi, Kazuo,Graci, Jason D.,Thompson, Corinne N.,Cameron, Craig E.,Watanabe, Masahiko
, p. 159 - 166 (2008/09/18)
One of the possible mechanisms of antiviral action of ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, 1) is the accumulation of mutations in viral genomic RNA. The ambiguous incorporation of 5′-triphosphate of ribavirin (RTP, 8) by a viral RNA-dependent RNA polymerase (RdRp) is a key step of the mutation induction. We synthesized three ribavirin analogues that possess hydrophobic groups, 4-iodo-1-β-D- ribofuranosylpyrazole-3-carboxamide (7a), 4-propynyl-1-β-D- ribofuranosylpyrazole-3-carboxamide (7b), and 4-phenylethynyl-1-β-D- ribofuranosylpyrazole-3-carboxamide (7c), and the corresponding triphosphates (9a, 9b, and 9c, respectively). Steady-state kinetics analysis of the incorporation of these triphosphate analogues by a poliovirus RdRp, 3D pol, revealed that while the incorporation efficiency of 9a was comparable to RTP, 9b and 9c showed lower efficiency than RTP. Antipolioviral activity of 7a and 7b was much more moderate than ribavirin, and 7c showed no antipolioviral activity. Effects of substituting groups on the incorporation efficiency by 3Dpol and a strategy for a rational design of more active ribavirin analogues are discussed.
Pyrazole-Related Nucleosides. Synthesis and Antiviral/Antitumor Activity of Some Substituted Pyrazole and Pyrazolo-1,2,3-triazin-4-one Nucleosides
Manfredini, Stefano,Bazzanini, Rita,Baraldi, Pier Giovanni,Guarneri, Mario,Simoni, Daniele,et al.
, p. 917 - 924 (2007/10/02)
Several pyrazole and pyrazolo-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-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-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.
