Antiviral Properties, Metabolism, and Pharmacokinetics of a Novel Azolo-1,2,4-Triazine-Derived Inhibitor of Influenza A and B Virus Replication

Karpenko, Inna L.; Деев, С. Л.; Киселев, О. И.; Charushin, Valery N.; Русинов, В. Л.; Ulomsky, Eugeney; Deeva, E. G.; Yanvarev, Dmitry V.; Ivanov, Alexander V.; Smirnova, Olga A.; Kochetkov, S. N.; Чупахин, О. Н.; Kukhanova, Marina K.

doi:10.1128/aac.01186-09

Cited by 67 publications

(35 citation statements)

References 34 publications

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“…As it was shown previously [15], triazavirine, being a guanine analogue, is a selective inhibitor of influenza RNA polymerase complexes. In addition, there are some data about its pleiotropic mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

“…The novel original drug that belongs to the azoloazine class of compounds, triazavirine (an analogue of purine nucleotide guanine), is licensed in Russia [15]. This drug was developed jointly by the scientists of Ural State Polytechnic University (Ekaterinburg, Russia), Postovsky Institute of Organic Synthesis (Ekaterinburg, Russia), and Research Institute of Influenza (St. Petersburg, Russia).…”

Section: Mir-journalorg Effect Of Triazavirine On Influenza and Secomentioning

confidence: 99%

“…1A) [15]. Oseltamivir phosphate (Ethyl (3R,4R,5S)-4-acetamido-5-amino-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate phosphate) (Fig.…”

Section: Compoundsmentioning

confidence: 99%

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Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

Ленева

Фалынскова

Махмудова

et al. 2018

Microbiology Independent Research Journal (MIR Journal)

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Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log 10 TCID 50 /ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Mir-journalorg Effect Of Triazavirine On Influenza and Secomentioning

confidence: 99%

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Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

Ленева

Фалынскова

Махмудова

et al. 2018

Microbiology Independent Research Journal (MIR Journal)

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“…With regard to the redox transformations of "Triazaverin" that we previously established that after the intragastric administration of laboratory animals of the drug substance, there is a reduction of the nitro group with the formation of 2-methylthio-6-amino-1,2,4-triazolo [5,1-c] [1,2,4]triazine-7-one [2], does not exhibit antiviral action in vitro and, most likely, which is not applicable metabolite.…”

Section: № 3 | 2015mentioning

confidence: 99%

“…Chimica Techno Acta cal properties of nitroazolo [5,1-c] [1,2,4] triazines [1] can assume various variants of metabolism: redox transformations in the body (directions A, B) as the reduction of the nitro group under the action of a reductases (direction A), oxidation of alkylthio fragment under the action of oxidases (direction B) and its further transformation. The part transferases under the action of N -and S-nucleophils, such as lysine, arginine, cysteine could lead to the replacement of alkylthio-or nitro groups (directions C, D).…”

Section: № 3 | 2015mentioning

confidence: 99%

The redox transformations and nucleophilic replacements as possible metabolic reactions of the drug “Triazaverin”. The chemical modeling of the metabolic processes

et al. 2015

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introductionThe relevance of creating new antiviral drugs due to the joint action of such operating factors as the spread of socially significant, particularly dangerous infections, and the emergence of pathogenic viral strains resistant to existing drugs.The antiviral drug "Triazaverin" and its analogues are highly effective in experiments in vivo and decreased activity in experiments on cell cultures, suggesting that the antiviral effect is not the "Triazaverin", and products of its transformations in the body. One way to identify such transformations in the organism is to predict the possible products of modifications of the compounds and chemical synthesis models.Based on the molecular structure of compounds 1a and study of chemi-

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Synthesis and Evaluation of Novel [1,2,4]Triazolo[5,1‐c][1,2,4]‐triazines and Pyrazolo[5,1‐c][1,2,4]triazines as Potential Antidiabetic Agents

Русинов

Сапожникова

Bliznik

et al. 2017

Archiv der Pharmazie

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Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers. From the two considered classes of heterocyclic compounds, the pyrazolotriazines showed the highest potency as antiglycating agents and DPP4 inhibitors. Structure-activity relationships (SAR) for these compounds, which can be considered as potential drugs for the treatment of type 2 diabetes, were evaluated.

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Antiviral Properties, Metabolism, and Pharmacokinetics of a Novel Azolo-1,2,4-Triazine-Derived Inhibitor of Influenza A and B Virus Replication

Abstract: Influenza viruses of types

Cited by 67 publications

References 34 publications

Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

The redox transformations and nucleophilic replacements as possible metabolic reactions of the drug “Triazaverin”. The chemical modeling of the metabolic processes

Synthesis and Evaluation of Novel [1,2,4]Triazolo[5,1‐c][1,2,4]‐triazines and Pyrazolo[5,1‐c][1,2,4]triazines as Potential Antidiabetic Agents

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