This review outlines the data of numerous studies relating to the broad-spectrum antiviral drug Triazavirin that was launched on the Russian pharmaceutical market in 2014 as an anti-influenza drug (the international non-patented name is Riamilovir). The range of antiviral activity of Triazavirin has been significantly expanded during recent years; in particular, it has been shown that Triazavirin exhibits activity against tick-borne encephalitis, Rift Valley fever, West Nile fever, and other infections of viral etiology. This drug has been approved for treatment of influenza and acute respiratory infections by the Russian Ministry of Health on the basis of comprehensive clinical trials involving over 450 patients. Triazavirin was found to be a highly effective and well-tolerated drug, allowing its over-the-counter sale. The recently published data on the use of Triazavirin in clinical practice for the treatment of patients with COVID-19 are discussed, with special attention paid to potential biological targets for this drug.
Non-xanthine inhibitors of the adenosine A2areceptor of the azoloazine series are good candidates for use as drugs for the treatment of neurodegenerative diseases and sepsis. This review systematizes and summarizes the structure – activity relationships in the series of triazoloazines, including annulated pyrimidines, pyrazines and triazines, as well as their tricyclic fused analogues. The above relationships for such systems are analyzed. The structures of the most efficient functional moieties from the point of view of affinity for the A2areceptor and selectivity for other types of adenosine receptors (A1, A2b, A3) are presented.The bibliography includes 71 references.
1 January 2020 in European Journal of Medicinal Chemistry
The present work reports on the synthesis of series of azolo[5,1‐ c ][1,2,4]triazines and derivatives of azoloazapurines. The synthesized compounds were tested in vitro for antibacterial activity against N. gonorrhoeae and antimycotic activity against Trichophyton interdigitale , Epidermophyton floccosum, Microsporum canis and Candida albicans . It was found that 10 compounds of the series of 3‐nitroazolo[5,1‐ c ][1,2,4]triazine‐4‐amines 4 exhibit high antibacterial activity (MIC≤15 μg/ml), but do not exhibit antimycotic activity. For compounds active against N. gonorrhoeae , a biological target was predicted from the pharmacophore search method and homologous modeling was carried out for it. The results of molecular docking using the constructed model of dihydrofolate reductase have a good correlation with in vitro tests. Refined docking showed the similarity of the leading compounds positions in the protein active site. The formation of stable non‐covalent bonds of the nitro group with the amino acid residues Lys34/Lys55 makes a major contribution to the orienting effect of ligands.