138787-01-6Relevant academic research and scientific papers
Design, synthesis and antiproliferative activity of methyl 4-iodo-1-β-D- ribofuranosyl-pyrazole-3-carboxylate and related compounds
Manfredini,Bazzanini,Baraldi,Simoni,Vertuani,Pani,Pinna,Scintu,Lichino,La Colla
, p. 1279 - 1284 (1996)
In a SAR study on azole-related nucleosides we have designed some pyrazole-nucleoside analogs characterised, for the first time, by a carboxylic ester moiety. 4-Iodo-1-β-D-ribofuranosyl-pyrazole-3-carboxylate showed a wide spectrum of antiproliferative activity and a particularly low cytotoxicity against resting PBL, being, unlike the other azole nucleosides, more active than the corresponding primary amide.
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.1 Design, synthesis and antiproliferative activity of methyl 4-iodo-1-β-D-ribofuranosylpyrazole-3-carboxylate (IPCAR), and derivatives, against human leukemias, lymphomas and solid tumors cell lines in vitro
Manfredini, Stefano,Bazzanini, Rita,Baraldi, Pier Giovanni,Simoni, Daniele,Vertuani, Silvia,Pani, Alessandra,Pinna, Elisabetta,Scintu, Franca,De Montis, Antonella,La Colla, Paolo
, p. 293 - 311 (2007/10/03)
A structure-activity relationship (SAR) study on some new 1-β-D-ribofuranosyl-3,4-substituted pyrazole derivatives led us to obtain 4-iodo-1-β-D-ribofuranosyl-pyrazole-3-carboxylate (3, IPCAR) and its 3-methyl-1,2,4-oxadiazole analog (11) at position C3. These compounds showed good potency, wide spectrum of antiproliferative activity and low cytotoxicity against resting peripheral blood lymphocytes (PBL). Although none of the test compounds displayed antiviral activity, IPCAR was able to potentiate the anti-HIV-1 activity of dideoxyinosine (ddI), thus behaving like the known inosine monophosphate dehydrogenase (IMPDH) inhibitors ribavirin and tiazofurin. The corresponding methyl esters of the latter two drugs (15 and 16) were also prepared, but they proved inactive. Overall, these results suggest that the target of IPCAR may be an enzyme other than IMPDH involved in the purine de novo biosynthesis.
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.
