Redox Conversions of 5-Methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4triazolo[1,5-a]pyrimidinide L-Arginine Monohydrate as a Promising Antiviral Drug

Abstract

This article presents the results of a study of electrochemical transformations in aqueous and aprotic media of 5-methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidinide l-arginine monohydrate (1a, Triazid) obtained by electrochemical methods and ESR spectroscopy. The effect of pH on the current and the reduction potential of 1a in an aqueous Britton–Robinson buffer solution was studied. It was found that 1a is irreversibly reduced in aqueous acidic media on a glassy carbon electrode in one stage with the participation of six electrons and the formation of 5-methyl-6-amino-7-oxo-1,2,4-triazolo[1,5-a]pyrimidin. The electroreduction of 1a in DMF on a background of tetrabutylammonium salts proceeds in two stages, controlled by the kinetics of second-order reactions. In the first stage, the reduction of 1a is accompanied by protonation by the initial compound of the basic intermediate products formed in the electrode reaction (self-protonation mechanism). The second quasi-reversible stage of the electroreduction 1a corresponds to the formation of a dianion radical upon the reduction of the heterocyclic anion 5-methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidin, which is formed upon the potentials of the first peak. The ESR spectrum of the radical dianion was recorded upon electroreduction of Triazid in the presence of Bu4NOH. The effect of the formation of ion pairs on the reversibility of the second peak of the 1a transformation is shown. A change in the rate and regioselectivity of the protonation of the dianion radical in the presence of Na+ and Li+ ions is assumed. The results of studying the electroreduction of 1a by ESR spectroscopy with a TEMPO trap make it possible to assume the simultaneous formation of both a nitroxyl radical and a radical with the spin density localized on the nitrogen at the 4 position of the six-membered ring.

Study of Different Carbonaceous Materials as Modifiers of Screen‐printed Carbon Electrodes for the Triazid as Potential Antiviral Drug

“…Since the formation of electroactive groups occurs during the functionalization of carbon black. It is possible that the single wave 6e process of TD reduction [12] is divided into 2 waves, corresponding, presumably, to the accession of 2 and 4 e [18,45,48,63]. This shape of the cathodic signal is unacceptable for analytical purposes.…”

“…Previously, we have found that TD is irreversibly reduced to one six‐electron wave with the formation 5‐methyl‐6‐amino‐7‐oxo‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐ a ]pyrimidinide l‐arginine. The reduction of the nitro group is accompanied by intermediates of a radical nature, which may be the reason for the appearance of biological activity in the substance [12]. Currently, multicenter clinical trials for influenza viruses are being carried out in clinics of the Russian Federation [10].…”

The electrochemical behavior’s character of a potential antiviral drug 3-nitro-4-hydroxy-7-methylthio-4H-[1,2,4]triazolo[5,1-c][1,2,4]triazinide monohydrate

“…Previously, we studied the redox transformations of substances of a number of triazolotriazines (Triazavirin® and Triazide) [18,19]. The studies demonstrated that the electrochemical behavior of a structural analog may differ due to the difference in the structure and requires an individual approach to the investigation of its redox mechanism.…”