Introduction: Cardiovascular diseases, including cardiomyopathies associated with endothelial dysfunction and impaired protein glycation, are the predominant cause of mortality in diabetes mellitus. This article presents data on the identification of functional and structural changes occurring during the development of diabetic cardiomyopathy and investigates the cardioprotective effects of the anti-glycating agents – the azolo-triazine derivative AB-19 and aminoguanidine. Materials and Methods: Diabetic cardiomyopathy was modeled using streptozotocin 45 mg/kg I.V. on 60 male Sprague-Dawley rats. Aminoguanidine was investigated at the dose of 50 mg/kg and compound AB-19 – 20 mg/kg once daily. Observations were conducted over a period of 12 weeks. Blood glucose levels and glycated hemoglobin concentration were monitored. Upon completion of the diabetic cardiomyopathy induction period, the following were studied: endothelioprotective properties, cardiac contractile activity, solubility of tail tendon collagen and morphological examinations of the heart and myocardial blood vessels. Results: The oral administration of AB-19 (20 mg/kg) and aminoguanidine (50 mg/kg) to animals with experimental diabetes mellitus resulted in a 17% reduction in blood HbA1c levels compared to that in the diabetic control rats. This treatment also limited the increase in AGEs in the blood by 51% and 39%, improved the solubility of collagen by 42% and 51%, respectively, restored endothelium-dependent vascular reactivity, and attenuated manifestations of left ventricular diastolic dysfunction associated with myocardial hypertrophy and fibrosis in diabetic animals. These findings were morphologically corroborated: animals treated with AB-19 and aminoguanidine exhibited a reduction in perivascular connective tissue, a decrease in collagen fibers in the myocardium, and a lower expression of AGEs and RAGE in IHC analysis using primary antibodies against AGEs and RAGE compared to the diabetic control group. Conclusion: Compound AB-19 (20 mg/kg once daily) attenuates functional and structural manifestations of diabetic cardiomyopathy.

A novel series of pyrrolo[1,2-f]azolo[1,5-a]pteridines has been synthesized via an efficient two-step annulation strategy. The photophysical properties of the resulting polyheteroaromatic fluorophores were systematically investigated in solution, solid state, and polymer films. In THF, the compounds exhibit intense emission in the visible region with high quantum yields (Ф up to 79.9

The electrochemical transformation of nitroheterocyclic compounds plays a critical role in understanding their biological activity. Despite structural similarities among nitrotriazolotriazines, their electroreduction mechanisms remain incompletely elucidated. This study focuses on the sodium salt of 3-nitro-4-hydroxy-7-methylthio-4H-[1,2,4]triazolo[5,1-c][1,2,4]triazinide monohydrate (TZV-OH), a structural analogue of the antiviral drug Triazavirin® (Riamilovir) – sodium salt of 3-nitro-4-oxo-7-methylthio-4H-[1,2,4]triazolo[5,1-c][1,2,4]triazinide dihydrate (TZV), and aims to investigate how structural differences affect the redox behavior of nitrotriazolotriazines. Using a combined experimental and computational approach, including cyclic voltammetry, chronoamperometry, electron paramagnetic resonance (EPR) spectroscopy, quantum chemical calculations, and preparative electrolysis with LC-HRMS analysis, we examined the electroreduction mechanism in both aqueous and aprotic media. Our findings reveal that TZV-OH undergoes a single-wave, diffusion-controlled, four-electron irreversible reduction of the nitro group, whereas TZV is reduced in two steps, complicated by a preceding chemical reaction. EPR spectroscopy confirms a higher concentration of radical intermediates for TZV-OH, supported by experiments with the DMPO spin trap and quantum chemical modeling. Mass spectrometry identified hydroxylamines, amines, and dimeric products as the primary products of the reduction process of TZV-OH. Quantum chemical calculations indicate that the formation of radical intermediates is thermodynamically more favorable for TZV-OH than for TZV, facilitating radical generation. These structural and mechanistic insights highlight the potential of TZV-OH as a superior antiviral agent. The integrated methodology outlined here serves as a predictive tool for assessing the pharmacological potential of nitrotriazolotriazines.

The series of new 2-substituted-5,7-di(het)aryl-6-nitro-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines were synthesized by reaction between imine and 1-substituted 2-nitroethylene derivatives. The structure of the obtained compounds including stereochemical configuration was confirmed by NMR techniques such as 1H, 13C, 2D 1H-1H (gNOESY), 1H-13C (gHSQC, gHMBC) 2D 1H-15N gHMBC and XRD method, additionally. For the obtained compounds, the signals of all hydrogen, carbon, and nitrogen nuclei in the NMR spectra were associated using two-dimensional NMR experiments. Based on the analysis of the spin-spin coupling constants (SSCC), it was found that the target compounds were obtained in the form of trans-trans isomers.

A novel chemotype of nitrile-containing azolopyrimidines with potential antitumor activity has been proposed, and a method for the synthesis of the corresponding 5-amino-7-oxoazolo[1,5-a]pyrimidine-6-carbonitriles by cyclocondensation of various aminoazoles and ethyl 2-cyano-3-R-amino-3-(methylsulfanyl)acrylates has been developed. Cytotoxic effects of the obtained azolopyrimidines against glioblastoma (A-172), bladder carcinoma (T-24), lung carcinoma (A-549), and human embryonic kidney (HEK-293) cells have been investigated, and structure-activity relationships have been identified. 2-Phenyl-5-(morpholin-4-yl)-7-oxo-1,2,4-triazolo[1,5-a]pyrimidine-6-carbonitrile 5j has been found to exhibit selective cytotoxic activity against the T-24 cells (IC50 = 14.68 µM), whereas 3-bromo-5-(morpholin-4-yl)-7-oxopyrazolo[1,5-a]pyrimidine-6-carbonitrile 5v has shown selective toxicity against the A-172 cells (IC50 = 18.38 µM). Further studies on heterocycle 5j in the annexin V apoptosis assay indicate that the primary mechanism involves inhibition of proliferative activity rather than induction of cell death. The cyclin-dependent kinase 2 protein is suggested as a possible target for the cytotoxic action of the studied compounds 5 on the T-24 cell line according to the notable correlation between docking studies and MTT assay results.

Azolo[1,5-a]pyrimidines (APs) are widely recognized as challenging scaffolds for diverse applications in both medicinal chemistry and materials science. Owing to their high potential, active research is focused on developing new derivatives through the derivatization and functionalization of their molecular structure. Herein, we report an unusual transformation in the AP series initiated by a hydroperoxide anion. The transformation proceeds via a nucleophilic attack by the hydroperoxide anion followed by the elimination of a cyanide anion, which subsequently reattacks the heterocyclic system, resulting in the formation of 7-(4-(dimethylamino)phenyl)-6-hydroxy-[1,2,4]azolo[1,5-a]pyrimidine-5-carbonitriles as unexpected nucleophilic transformation products in yields of 55-72%. Mechanistic studies employing computational, chemical, and optical methods allow the most probable pathway for the reaction process to be identified. Furthermore, the new series of prepared APs in this way demonstrates the opportunity for postsynthetic transformations, including alkylation, acylation, Mitsunobu reaction, Ritter reaction, hydrolysis, and salt formation.

Azolo[1,5- a ]pyrimidines represent an important class of nitrogen-containing heterocycles due to a wide range of useful properties.

The electrochemical behavior of sodium 5-(7-amino-3-cyanopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-2-ide (compound 1) as a promising inhibitor of casein ki-nase 2, a novel target in anticancer therapy, was investigated for the first time. Compound 1 undergoes irreversible electrooxidation on a glassy carbon electrode (GCE) in aqueous media, producing two poorly resolved peaks caused by amino group oxidation. The first oxidation step, involving a two-electron transfer, is diffu-sion-controlled and complicated by a preceding chemical reaction. The peak current of the first oxidation step of the amino group of compound 1 in the potential range 0.0–1.25 V was used as the response. The influence of voltammetric mode, electro-lyte pH, potential scan rate, accumulation time and potential on the oxidation peak current of compound 1 was studied. A method of compound 1 quantification by di-rect differential pulse voltammetry was developed. The peak current obtained in 0.1 M KCl was linearly related to the compound 1 concentration in the range of 0–160 mg/L with the determination coefficient of 0.999. The method provided a detection limit of 1.9 mg/L and recovery close to 100%.

The C-H functionalization strategy was first applied to the Cu-mediated radical arylation reactions of triazolotriazines with aromatic diazonium salts. A series of C(3)-modified triazolo[5,1-c][1,2,4]- triazines were obtained in yields of up to 80% under mild conditions. The radical nature of the reaction mechanism was established by the TEMPO radical trap experiments. The developed method is characterized by its versatile application opportunities, particularly it allows C(3)arylated azoloazine-derived compounds of various architectures to be available. The elaborated synthetic strategy is of interest in the directed design of azaheterocyclic biomolecules with diverse pharmacological applications.

A novel chemotype of nitrile-containing azolopyrimidines with potential antitumor activity has been proposed, and a method for the synthesis of the corresponding 5-amino-7-oxoazolo[1,5- a ]pyrimidine-6-carbonitriles by cyclocondensation of various aminoazoles and ethyl 2-cyano-3-R-amino-3-(methylsulfanyl)acrylates has been developed. Cytotoxic effects of the obtained azolopyrimidines against glioblastoma (A-172), bladder carcinoma (T-24), lung carcinoma (A-549), and human embryonic kidney (HEK-293) cells have been investigated, and structure–activity relationships have been identified. 2-Phenyl-5-(morpholin-4-yl)-7-oxo-1,2,4-triazolo[1,5- a ]pyrimidine-6-carbonitrile 5j has been found to exhibit selective cytotoxic activity against the T-24 cells (IC 50  = 14.68 µM), whereas 3-bromo-5-(morpholin-4-yl)-7-oxopyrazolo[1,5- a ]pyrimidine-6-carbonitrile 5v has shown selective toxicity against the A-172 cells (IC 50  = 18.38 µM). Further studies on heterocycle 5j in the annexin V apoptosis assay indicate that the primary mechanism involves inhibition of proliferative activity rather than induction of cell death. The cyclin-dependent kinase 2 protein is suggested as a possible target for the cytotoxic action of the studied compounds 5 on the T-24 cell line according to the notable correlation between docking studies and MTT assay results.

The novel chemotype, azolo[5',1':2,3]pyrimido[5,4-e]tetrazolo[1,5-c]pyrimidines 12, with promising dual action antiglycating and α-glucosidase inhibiting activities was developed basen on reaction of 6-(tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines 3 with (het)aroyl chlorides. The conditions for this process were optimized to achieve high yields of heterocycles 12 upon mild conditions whereas azido-tetrazole tautomerism was revealed for these products 12 and it was shown that the equilibrium is shifted towards azide tautomer. The obtained azolo[5',1':2,3]pyrimido[5,4-e]tetrazolo[1,5-c]pyrimidines 12 inhibited the glycation reaction in the BSA-glucose assay more strongly than pyridoxamine as a reference compound, which is promising in terms of preventing AGEs assosiated pathologies such as long-term complication of diabetes and cancer. Furthermore, some heterocycles 12 inhibited α-glucosidase in the mid-micromolar range - more effectively than acarbose, with an IC50 17.52 μM for the lead compound 12k.

A regiospecific synthesis of N9‐alkylated purines as novel acyclic nucleosides was developed. This approach is based on reconstructive methodology involving the construction of a target heterocyclic scaffold on a readily available 5‐aminotetrazole moiety, which is subsequently cleaved under reductive conditions due to azido‐tetrazole tautomerism. It appeared that the rate of reduction for the azide fragment in 6‐nitro‐7‐alkylaminotetrazolo[1,5‐a]pyrimidines is much greater than the rate of nitro group reduction. Treatment of these heterocycles with hydrogen over a palladium catalyst resulted in the formation of triaminopyrimidines in excellent yields through the reduction of both the azide and nitro group. Triaminopyrimidines were transformed into the desired N9‐alkylated purines, and an analog of the marketed drug penciclovir was synthesized by the developed method.

A method for the synthesis of new 7-(substituted amino)-5-methylthioazolo[1,5-a]pyrimidines a ]pyrimidines has been developed. Based on the MTT test, IC50 50 values were calculated for the obtained compounds against lung carcinoma (A549), liver carcinoma (HepG2), embryonal rhabdomyosarcoma (Rd) and human embryonic kidney (HEK 293) cell lines. Some compounds from the series demonstrated activity close to the reference drug, but with a certain selectivity. Based on the results of MTT assay and molecular docking studies for the catalytic subunits of PI3K, two isoforms (PI3K beta and PI3K delta) were assumed as the targets for the new series of azolo[1,5-a]pyrimidines a ]pyrimidines with cytotoxic effect on the rhabdomyosarcoma cell line.

An overview of the main scientific achievements of Russian universities in the field of organic chemistry over the period 2018–2023 is presented.

The applicability of SNH and click reactions in the series of 2-amino-5-bromomethyl-3-(ethoxycarbonyl)pyrazine 1-oxide and its derivatives for the synthesis of distant analogs of folic acid and fluorophores was studied. The target products were synthesized in the yields up to 81

A method was developed for the synthesis of compounds of a new series of 5,7-diaryl-6-nitro-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines under the conditions of the Michael reaction between the corresponding triazole-containing Schiff bases and β-nitrostyrene derivative followed by additional heterocyclization. The oxidation of the resulting tetrahydro derivatives with manganese(iv) oxide made it possible to prepare previously unknown functional derivatives of 2-substituted 5,7-bis(4-methoxyphenyl)-6-nitro-1,2,4-triazolo-[1,5-a]pyrimidines, whose structures were determined using NMR correlation spectroscopy (1H—1H NOESY, 1H—13C HMBC).

New 7-amino-6-nitro-substituted [1,2,4]triazolo- and pyrazolo[1,5-a]pyrimidines a ]pyrimidines were synthesized by an alternative strategy based on amino azoles and 2-nitro-3(p-tolylamino)acrylonitrile. p-tolylamino)acrylonitrile. Unexpectedly, 3,5-dinitro-N- N- (p-tolyl)pyridine-2,6-diamine p-tolyl)pyridine-2,6-diamine was formed when the starting 5-amino-1,2,4-triazoles contained NO2 2 or CF3 3 substituents. O2N H2N

Polyvinyl chloride (PVC) plays an important role in industry; however, due to its uncontrolled accumulation in the environment, the methods for its utilization are of high demand. Herein we wish to report an approach for the utilization of PVC via its use as a carrier for some azole-based drugs, such as 2-mercaptobenzothiazole (multi-activity drug), 4-oxo-1,4-dihydropyrazolo[5,1-c]-1,2,4-triazine-3,8-dicarboxylic acid diethyl ester (antidiabetic drug) and 5-methyl-6-nitro-7-oxo-1,2,4-triazolo[1,5-a]pyrimidinide (antiviral drug). The abovementioned approach involves the reaction between PVC and potassium or sodium salts of these azole-based drugs either in solution or under ball-milling conditions. The as-obtained PVCs modified with azole-based drugs were isolated for the first time and characterized by means of 1H NMR-spectroscopy as well as gel-permeation chromatography (GPC).