Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using Purine Nucleoside Phosphorylase.

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task.

Enzymatic synthesis of novel purine nucleosides bearing a chiral benzoxazine fragment.

A series of ribo- and deoxyribonucleosides bearing 2-aminopurine as a nucleobase with 7,8-difluoro- 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (conjugated directly or through an aminohexanoyl spacer) was synthesized using an enzymatic transglycosylation reaction. Nucleosides 3-6 were resistant to deamination under action of adenosine deaminase (ADA) Escherichia coli and ADA from calf intestine. The antiviral activity of the modified nucleosides was evaluated against herpes simplex virus type 1 (HSV-1, strain L2).

New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1.

Using the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient.

Phosphoramidate derivatives of acyclovir: synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro.

The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM.