Timofey D. Moseev

A convenient approach toward 4-carboranylcoumarins from 3-bromocoumarins via a one-pot Michael addition–elimination sequence is reported. The obtained 4-isomers was found to display a red-shifted absorption over 3-substituted because of carborane-induced steric hindrance. While amino derivatives demonstrated rotatable excited-state dynamics governing their aggregation-induced emission, the methoxy analog exhibited unique room-temperature phosphorescence of 0.7 μs. This derivative showed strong dual-emission aggregation in 99% water, providing the molecular design of organic–inorganic materials for application in molecular electronics.

An application of vinylacetylene ortho-carborane derivatives in multicomponent reactions involving aldehydes, amines, and acetylenes (A³), as well as the optimization of conditions for obtaining target compounds and the scope of application of the methodology were studied. Six novel molecules of propargylamines containing (hetero)aromatic substituents were synthesized in yields of 15–70%. The results obtained could be used in the targeted synthesis of hybrid organo-inorganic functional materials, and also biologically active compounds based on ortho-carborane.

An efficient method based on the nucleophilic functionalization of nonaromatic 2 H ‐imidazole 1‐oxides with carbonyl compounds has been developed for the first time to afford a wide range of azaheterocyclic enaminonic compounds of various architectures in yields of up to quantitative. It has been found that the reaction proceeds via a nucleophilic hydrogen substitution (S _N ^H AE) mechanism, in which sodium sulfide (Na ₂ S) serves as a base, generating an active carbanion. The enaminone derivatives can be deprotonated to result in the promising dimeric molecular systems. The postmodification of enaminones containing a CBr bond has also been carried out via the Suzuki–Miyaura cross‐coupling reaction. The obtained compounds are of interest in the design of pharmacologically active compounds ligands and building blocks of functional materials.

In this work, a synthetic strategy based on the reaction of 5-bromo-2-(4-fluorophenyl)-4-methyl-2H-1,2,3-triazole with various thioaromatic derivatives were applied to afford a series of thioether derivatives of 1,2,3-triazole-N-oxides in yields of 52–80%. The obtained compounds were shown to be characterized by low cytotoxicity towards human embryonic kidney (HEK293) cells with IC50 values ranging from 128 to 76 µM and high toxicity towards malignant rhabdomyosarcoma cancer (Rd) cells with IC50 values ranging from 93 to 22 µM. These compounds were screened for the ability to induce nitric oxide production in cells via DAF-FM fluorescence. Several compounds demonstrated a twofold increase in nitric oxide levels relative to the control. Two leader molecules demonstrating the lowest cytotoxicity values and the effect on nitric oxide production in rhabdomyosarcoma cells were identified. Thus, the method could be considered as a convenient one for qualitative or semi-quantitative determination of nitric oxide in a screening process of large number of compounds to define lead molecules capable of influencing nitric oxide production.

The dual reactivity of 5-aryl-4H-imidazol-3-oxides with respect to carboranyllithium has been studied. In particular, in the presence of an oxidizing agent, the reaction of nucleophilic substitution of hydrogen by the mechanism of addition-oxidation (S_N^H AO) occurs with yields of up to 95%. On the other hand, in the absence of an oxidizing agent, the nucleophilic addition (A_N) processes take place with yields of up to 60% at C(5) and C(2) carbon atoms of the imidazole ring, with predominance of the C(5) products in the case of ortho-carboranillitium, and C(2) in the case of 1-phenyl-ortho-carboranillitium. The behavioral characteristics of the A_N reaction were studied using quantum chemical calculations and the reaction energy diagram. In addition, in the case of N-oxide derivatives, a mild light-induced transformation was found to yield oxaziridine cyclic structures characterized by enhanced thermal stability. The obtained data on the reactivity of nonaromatic imidazole systems toward carboranyllithium are of interest in the design of advanced hybrid organic-inorganic functional materials.

An original, transition metal-free, two-step synthetic strategy based on sequential S_N ^H and S_N ^Ar reactions, namely C–H functionalization of nonaromatic 2H-imidazole 1-oxide with pentafluorophenyl lithium followed by aromatic fluorine substitution with arylthioles, was proposed. A series of new arylthio-tetrafluorobenzene-imidazole triad multifunctional compounds were prepared in good yields of 62–94%. The in silico study of the synthesized triads toward biotargets associated with endothelial dysfunction (PDE5a); cancer (EGFR, CDK2); and SARS-CoV-2 viral infection (M^pro) revealed that biotarget binding selectivity was highly sensitive to the positioning of substituents on the aromatic ring. The synthesized triads could be considered as perspective lead compounds in the design of agents for pharmaceutical applications. Received: 04 September 2025 Accepted after revision: 12 November 2025 Article published online: 09 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Introduction: Osteoporosis is an important medical and social public health problem in an aging or elderly society, the issue of pharmacological correction of which remains unresolved to this day. Materials and Methods: A design of prospective 11β-HSD1 inhibitors was performed on the basis of the literature data. A virtual screening of the designed compounds was performed using pharmacophore searching (DataWarrior, Flexophore), pharmacophore alignment (PhESA), and molecular docking (Jamda). 2D protein-ligand interaction maps were generated using PoseEdit, and 3D visualizations were produced in VMD. The cytotoxicity of the compounds was assessed in HEK-293 cells across a concentration range of 8–1024 μM, with IC50 values calculated in RStudio. Results and Discussion: A comprehensive virtual screening of prospective 11β-HSD1 inhibitors was performed, incorporating pharmacophore searching, PhESA alignment, and molecular docking against the 11β-HSD1 complex (PDB: 4YYZ). Several compounds (TS-897, TS-883, TS-945, and others) demonstrated Jamda Score values comparable to or exceeding that of the native ligand, indicating strong predicted binding affinity. Additional candidates were identified based on high pharmacophore similarity (>0.95). Among the 14 proposed compounds, four (IV-81, IV-91, IV-158) exhibited no cytotoxicity in HEK-293 cells (IC50 > 1024 µM). These findings support the potential of the synthesized azoloazine derivatives as novel 11β-HSD1 inhibitors for further in vitro and in vivo studies in osteoporosis therapy. Conclusion: As a result of this work, original azoloazine derivatives have been developed for further biological testing aimed at regulating the activity of 11β-hydroxysteroid dehydrogenase isoforms (11β-HSDs) for pharmacological correction of bone remodeling and osteoreparation disorders.

A metal-free synthetic strategy based on the cycloaddition reaction of oxamoyl chlorides to vinylacetylene o-carborane toward photoactive molecular systems bearing both vinyl-conjugated C-substituted o-carborane and isoxazole moieties is reported. The elaborated compounds exhibit absorption in the range of 250–300 nm with ε > 10⁴ cm^–1·M^–1, but their emission varies greatly depending on the type of substituent at the C3 position of the isoxazole and does not demonstrate the solvatochromic characteristics typically associated with classical push–pull fluorophores. Incorporation of methoxy groups into the o-carborane–isoxazole dyads allows the design of an acceptor–π-conjugation–donor system (A–π–D), which is more efficient in light of intermolecular charge transfer (ICT) effects compared to the similar 1,2,3-triazole ones. Photoactive molecules with p-chlorophenyl and 2-(trifluoromethoxy)phenyl substituted in toluene have intense emissions of TICT states and PLQY up to 91%. Meanwhile, the 2-naphthyl-substituted molecule demonstrates dual-emission behavior in the 330–560 and 660–800 nm region with QY of 83 and 62%, respectively. Thus, the cycloaddition reactions of N-centered 1,3-dipoles to vinylacetylene o-carborane can be regarded as a promising synthetic approach in the design of advanced materials. Received: 03 July 2025 Accepted after revision: 01 September 2025 Article published online: 24 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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.

The aim. To study the acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles.Materials and methods. The study was performed on white laboratory female BALB/c mice (n=57) and male C57Bl/6 mice (n=66). Acute toxicity was assessed according to the interstate standard GOST 32644-2014 with histological evaluation of internal organs. Endothelial dysfunction was modeled by 7-day intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME). The studied small molecules were administered intragastrically using a probe. To assess the endothelial protective effect, the levels of systolic and diastolic blood pressure were evaluated, as well as the coefficient of endothelial dysfunction; for the cardioprotective effect, the results of stress tests on the myocardium were evaluated.Results. The study of acute toxicity of the studied small molecules allowed us to classify them as class 4 and 5. The administration of compounds 1(a–d) and 2(a–c) to mice at a dose equal to 1/10 of LD50 led to changes in blood pressure and restoration of the dynamics of pharmacological tests in response to the administration of acetylcholine and sodium nitroprusside. Molecules 1b and 2c showed statistically significant endothelial protective activity in 3 doses (1/10, 1/50 and 1/100 of LD50). Also, these hit compounds demonstrated cardioprotective effects, recorded by the restoration of the functional capabilities of the myocardium in response to load and in the adrenoreactivity test, and to a lesser extent, during resistance exercise.Conclusion. The studied compounds have low toxicity and have endothelial- and cardioprotective effects. This study may contribute to the formation of an idea about further directions in the study of the pharmacological activity of these molecules from the group of phenolic and thiophenolic derivatives of 2H-imidazoles.