Approaches to the synthesis of heterocyclic C-nucleosides

This review is focused on the synthetic strategies to heterocyclic C-nucleosides and covers the literature from 2011 to 2021. The main attention is paid to the following three approaches: the direct C—C coupling of a carbohydrate moiety with a preformed aglycon unit, the construction of a (pseudo)sugar residue on a pre-formed aglycon, and the construction of an aglycon on a pre-formed (pseudo)sugar. In each Section, the literature data are categorized in terms of the size of aglycon from simple to complex, the advantages and drawbacks of the reviewed approaches are discussed. © 2023, Springer Science+Business Media LLC.Russian Science Foundation, RSF: 22-23-00282This work was financially supported by the Russian Science Foundation (Project No. 22-23-00282)

Nitroazolopyrimidines – Attractive Structures in Medicinal Chemistry

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

Cyanmorpholinoethylene in the synthesis of relevant azoloazines

Approach to the synthesis of promising azolopyrimidines containing a primary amino group by reactions of variously substituted aminoazoles with cyanmorpholinoethylene was developed. © 2019 Author(s)

Atom-efficient synthesis of hybrid molecules combining fragments of triazolopyrimidines and 3-ethoxycarbonyl-1-ethyl-6-fluoroquinolin-4(1H)-one through 1,2,3-triazole linker

[Figure not available: see fulltext.] An atom-efficient method toward hybrid molecules via azide-alkyne cycloaddition of 7-azido-3-ethoxycarbonyl-1-ethyl-6-fluoroquinolin-4(1H)-one and novel perspective triazolopyrimidines has been developed. This procedure features mild conditions and a broad substrate scope including hydrophobic and hydrophilic triazolopyrimidines. The synthesized hybrid structures combine fragments of fluoroquinolone with proved antibacterial activity and triazolopyrimidines, which may act as structural analogs of adenosine receptor effectors or antiviral azoloazine heterocycles. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.Russian Foundation for Basic Research, РФФИ: 18-03-00787 АWe wish to thank the Russian Foundation for Basic Research for financial support (grant 18-03-00787 А)

Cyanmorpholinoethylene in the Synthesis of Relevant Azoloazines

The results were obtained within the framework of the state task of the Ministry of education and science of Russia (4.6351.2017/8.9) and with the financial support of the Russian science Foundation (№ 17-13-01096)

Azoloazines as Perspective Antiglycating Agents for Therapy of Diabetes Complications

This work was supported by Russian Federation Ministry of education and science (grant № 4.6351.2017/8.9) and Russian Foundation for Basic Research (grant № 18-03-00787)

2-Furyl-6-nitro-1,2,4-triazolo [1,5-a]pyrimidin-7-one

A sodium salt of 2-(fur-2-yl)-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7-one as a close structural analogue of ZM-241385 was obtained. This heterocycle can serve as an effector for A2a adenosine receptors and possesses antiseptic activity. The structures of compounds were confirmed based on the data of 1H, 13C NMR spectroscopy, IR spectroscopy, and an elemental analysis. The structure of sodium salt 2-furyl-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7-one was confirmed by an X-ray diffraction analysis. © 2023 by the authors.Ministry of Education and Science of the Russian Federation, MinobrnaukaThe research funding from the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority-2030 Program) is gratefully acknowledged

6-Aminotriazolo[1,5-a]pyrimidines as precursors of 1,2,4-triazolo[5,1-b]purines

Triazolo[5,1-b]purines are rare structural analogues of natural nucleosides and nucleobases purine series. At the same time, prominent representatives of azolopurines exhibit a broad spectrum of antiviral effect, activity against of rheumatoid arthritis, psoriasis, Alzheimer’s, Parkinson’s and etc. Despite the practical value azolo[5,1-b]purines extremely sparingly represented in the chemical literature, due to the complexity of their synthesis. We suggest a convenient way to synthesize triazolopurines with aminotriazolo[1,5-a]pyrimidines (2) as available starting compounds obtained in good yield by reduction of nitro derivatives (1).The work was supported by RFBR grant 13-03-0086

Azolo[1,5-a]pyrimidines and Their Condensed Analogs with Anticoagulant Activity

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This research was funded within the framework of the grant agreement as government subsidies from the federal budget in accordance with paragraph 4 of article 78.1 of the Budget Code of the Russian Federation (Moscow, 1 October 2020, No. 075-15-2020-777)

The Effects of Nitroazolopyrimidines on the A1 Adenosine Receptor and Intraocular Pressure in Rats

Abstract: Six compounds of the 5(7)-alkylamino-6-nitroazolopyrimidine and 8-alkylazolo[5,1-b]purine series were selected based on the structural analysis of A1 adenosine receptor inhibitors and the role of this biological target in the modulation of intraocular pressure, an important factor in the pathogenesis of glaucoma. These heterocycles were shown to exhibit a weak affinity towards the A1 adenosine receptor on an in vitro model of the adenosine-dependent change of the chronotropic effect on isolated atria of white mice. On the other hand, thiadiazolo[3,2-a]pyrimidines and triazolo[5,1-b]purine displayed an in vivo hypotensive effect in rats. The leading compound, 5-methyl-8-(hydroxyethyl)triazolo[5,1-b]purine) (0.2% solution), caused a 34% reduction of ophthalmotonus in 3 h without an adverse resorptive effect. In addition, using the MTT-test it was shown on the human HepG2 cell line that the heterocycles affecting the intraocular pressure were by one to two orders of magnitude less cytotoxic than the reference doxorubicin. © 2022, The Author(s).Ministry of Education and Science of the Russian Federation, Minobrnauka, (075-15-2020-777)The work was supported by the Ministry of Science and Higher Education of the Russian Federation, project no. 075-15-2020-777