X-Ray Crystallographic and Kinetic Analysis of Human Purine Nucleoside Phosphorylase Complexes with 1-β-D-Ribofuranosyl-1,2,4-triazole-3-carobxamide and 1-β-D-Ribofuranosyl-1,2,4-triazole-3-carboxamidine

Synthesis of 4-substituted-1,2,3-triazole carbanucleoside analogues of ribavirin via click chemistry

“…Interesting therapeutic properties have also been found in structurally related analogues of 1, by introduction of modifications at position 4 of the heterocycle, for example brenedin (Mizoribine R , 2) used as an immunosuppressor for the treatment of transplant patients, 2 or EICAR (3), which causes depletion of purine nucleotides, resulting in a broad spectrum of activity against RNA and DNA viruses and tumour cell proliferation. 3 As the result of modifications in other positions of the heterocyclic ring of 1, new compounds were developed such as ribavirin (Virazole R , 4), 4 used for the treatment of RSV infections, lassa fever, hepatitis (A, B, and C), measles and mumps, and its analogue TCNR (5), a better substrate for human PNP than ribavirin, due to the interaction of the protonated carboxamidine group with the Asn 243 and Glu 201 residues in the PNP active site. 5 A great number of 1,2,3-triazole derivatives have also been reported as potent antiviral, antimicrobial or antiproliferative agents, 6-8 some interesting examples of the 1,2,3-triazole nucleosides being compounds 6 and 7, which exhibit anti-HIV activity 9 and cytostatic activity, 10 respectively.…”

“…3 As the result of modifications in other positions of the heterocyclic ring of 1, new compounds were developed such as ribavirin (Virazole R , 4), 4 used for the treatment of RSV infections, lassa fever, hepatitis (A, B, and C), measles and mumps, and its analogue TCNR (5), a better substrate for human PNP than ribavirin, due to the interaction of the protonated carboxamidine group with the Asn 243 and Glu 201 residues in the PNP active site. 5 A great number of 1,2,3-triazole derivatives have also been reported as potent antiviral, antimicrobial or antiproliferative agents, 6-8 some interesting examples of the 1,2,3-triazole nucleosides being compounds 6 and 7, which exhibit anti-HIV activity 9 and cytostatic activity, 10 respectively. Also in the field of carbanucleosides (substances in which the anomeric oxygen of furanose ring is replaced by a methylene group), the synthesis and biological evaluation of compounds having a 1,2,3-triazole ring as a nucleobase have been reported recently; in the case of 8 moderate antiviral activity against HIV-1 (IC 50 43.8 lM) has been found, 11 while 9 showed potent antiviral activity against vaccinia virus (EC 50 0.4 lM), but moderate activity against cowpox virus (EC 50 39 lM) and severe acute respiratory syndrome coronavirus (SARCoV) (EC 50 47 lM).…”

A New 1,2,4-Triazole Acyclonucleosides: Synthesis and Biological Evaluation

“…The higher activity of this molecule against herpes virus [2] pushed the researchers to find a molecule similar but which is less toxic than the ribavirin. In fact, several new 1,2,4-triazole nucleosides were carried [3][4][5][6][7][8][9][10][11]. With this in mind, we explored the synthesis of two novel 1,2,4-triazole acyclonucleosides.…”