Biopolymers and cell. 2006; 22 (6): 468 - 474

Nucleosides with tricyclic aglycone. I. The ribonucleosides of condensed 1,2,4-triazine: synthesis and its antiherpetic activity.

I.V. Alexeeva, L.G. Palchikovskaya, S.L. Rybalko, L.S. Usenko, A.S. Kobko, L.A. Popova, S.T. Dyadun, A.D. Shved

The method of synthesis of tricyclic aglicones based on the condensed 1,2,4-triazine has been developed to perform their ribosylation by the simplified procedure (technique) of silylic condensation. The identity and structure of the resultant compounds were ascertained through chromatography, UV, PMR, and mass-spectrometry. High tautomeric status of 3-oxo-(3-thioxo)-triazinebenzothiazines (I and II bases) may promote formation of two regioisomeric nucleosides. The introduction of alkylmercapto-substituent into position 3 of triazine fragment of aglicone molecule stabilizes tautomeric form with proton in triazine cycle, thus it allows achieving the regiospecificity of the process. Research on the toxicity and antiherpetic activity of the synthesized compounds (bases and nucleosides) was carried out in RK-13 tissue culture. It was demonstrated that 3-oxo-triazinebenzothiazine (base I) proved to be the least toxic and the most effective with respect to herpes virus (HSV-2), the selectivity index of which exceeded that of acyclovir (Virolex) significantly.

Key words: abnomal nucleosides, tricyclic aglicones, herpes virus of the 2nd type (HSV-2), antivirus agents.