Nucleophilic Substitution of Nitro Group in Dihydroazole[5,1-c][1,2,4]triazines

This work was supported by the Russian Foundation for Basic Research, project # 19-33-90086

Nitroazolopyrimidines – Attractive Structures in Medicinal Chemistry

We thank Russian Foundation for Basic Research (grant № 18-03-00787) for financial support

Oxidative Aromatization of 4,7-dihydro-6-nitroazolo[1,5-a] Pyrimidines: Synthetic Possibilities and Limitations, Mechanism of Destruction, and the Theoretical and Experimental Substantiation

The reaction tolerance of the multicomponent process between 3-aminoazoles, 1-morpholino2-nitroalkenes, and aldehydes was studied. The main patterns of this reaction have been established. Conditions for the oxidation of 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines were selected. Previous claims that the 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines could not be aromatised have now been refuted. Compounds with an electron-donor substituent at position seven undergo decomposition during oxidation. The phenomenon was explained based on experimental data, electro-chemical experiment, and quantum-chemical calculation. The mechanism of oxidative degradation has been proposed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: The synthetic part was supported by the Ministry of Science and Higher Education of the Russian Federation, State Contract no FEUZ-2020-0058 (H687.42B.223/20). The electrochemical research and the quantum chemical calculations was funded by Russian Foundation for Basic Research (RFBR), project number 20-03-00814

Detection of Anti-viral Drug Riamilovir and Herbicides in Aqueous Media by Using Pyrene-based Fluorescent Chemosensors

Two ethyleneglycol esters of 1-pyrene carboxylic acid were studied as chemosensors for the fluorescence “turn-off” detection of two nitro-containing analytes, such as antiviral drug Riamilovir (Triazavirin ®) and herbicidal agent dinitro-ortho-cresol (DNOC). In both cases the dramatic fluorescence quenching was observed with quenching constants as high as 3·104 M-1 and limits of detection (LOD) as low as 100 ppb

Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

[Figure not available: see fulltext.] The review presents data on the synthesis as well as studies of biological activity of new derivatives of pyrimido[1,2-a]benzimidazoles published over the last decade. The bibliography of the review includes 136 sources. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.The reported study was funded the RFBR, project No. 19-33-90161

Methods of Synthesis and Antiviral Activity of New 4-Alkyl-3-Nitro-1,4-Dihydroazolo[5,1-c][1,2,4]Triazin-4-ols

[Figure not available: see fulltext.] An azo coupling reaction of α-nitro ketones with 5-diazoazoles was used to obtain 4-alkyl-3-nitro-1,4-dihydroazolo[5,1-с][1,2,4]triazines, which were characterized with respect to their antiviral activity against influenza and Coxsackie B3 viruses. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.This study was funded by the Russian Science Foundation (project No. 20-13-00142)

CK2 Inhibition and Antitumor Activity of 4,7-Dihydro-6-nitroazolo[1,5-a]pyrimidines

Today, cancer is one of the most widespread and dangerous human diseases with a high mortality rate. Nevertheless, the search and application of new low-toxic and effective drugs, combined with the timely diagnosis of diseases, makes it possible to cure most types of tumors at an early stage. In this work, the range of new polysubstituted 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines was extended. The structure of all the obtained compounds was confirmed by the data of 1H, 13C NMR spectroscopy, IR spectroscopy, and elemental analysis. These compounds were evaluated against human recombinant CK2 using the ADP-GloTM assay. In addition, the IC50 parameters were calculated based on the results of the MTT test against glioblastoma (A-172), embryonic rhabdomyosarcoma (Rd), osteosarcoma (Hos), and human embryonic kidney (Hek-293) cells. Compounds 5f, 5h, and 5k showed a CK2 inhibitory activity close to the reference molecule (staurosporine). The most potential compound in the MTT test was 5m with an IC50 from 13 to 27 µM. Thus, our results demonstrate that 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines are promising for further investigation of their antitumor properties. © 2022 by the authors.Ministry of Education and Science of the Russian Federation, Minobrnauka: FEUZ-2020–0058, H687.42B.223/20This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation, State Contract № FEUZ-2020–0058 (H687.42B.223/20)

Особенности нуклеофильного замещения нитрогруппы в 4-алкил-6-нитро-1,2,4-триазоло[5,1-c][1,2,4]триазинах

The nucleophilic substitution of the nitro group of 4-alkyl-6-nitro-4,7-dihydro-1,2,4-triazolo[5,1-c][1,2,4]triazine-7-ones on the example of interactionwith morpholine was studied. It is established that under the action of excess cycloalkylimine at room temperature the unusual easy disclosure of triazine cycle with the formation of sterically hindered hydrazones occurs which are the key intermediates for further transformations. The carrying of reaction at elevated temperatures leads to the formation of products of substitution of the nitro group with the amine and also with morpholyl hydrazones which are the products of hydrolysis of amides of hydrazones and subsequent decarboxylation. Thus, the nucleophilic substitution of the nitro group in the described triazolotriazines flows through the ANRORC mechanism.Исследовано нуклеофильное замещение нитрогруппы в 4-алкил-6-нитро-4,7-дигидро-1,2,3-триазоло[5,1-с][1,2,4]триазин-7-онах на примере взаимодействия с морфолином. Установлено, что под действием избытка циклоалкилимина при комнатной температуре происходит необычно легкое раскрытие триазинового цикла с образованием пространственно затрудненных гидразонов - ключевых интермедиатов для дальнейших превращений. Проведение реакции при повышенных температурах приводит к образованию продуктов замещения нитрогруппы амином, а также морфолилгидразонов - продуктов гидролиза амидов гидразонов и последующего декарбоксилирования. Таким образом, нуклеофильное замещение нитрогруппы в описанных триазолотриазинах протекает по механизму ANRORC

The way of excipients finding during tablet form preparation

There are several ways of excipients selection during tablets preparation. Experiment planning is one of them. We had three factors (fillers, binders and disintegants) and found their rational proportion. In summary we chose optimal excipients - sorbitol, hypromellose, aerosil, magnesium stearate, sodium starch glycolate