Ramil F. Fatykhov

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.

A heptafluorobutyric acid-induced cross-dehydrogenative coupling reaction of arylamines with 1,2,4-triazines has been described. This metal-free protocol enables regioselective para-C–H hetarylation of diverse arylamines including well-known fluorophore scaffolds, such as triphenylamine, carbazole, and phenothiazine, with easily accessible 1,2,4-triazines under mild conditions. This approach has potential for drug development and material design.

A novel PASE-oriented synthesis of quaterpyridines via 1,2,4-triazine dimerization and inverse electron-demand Diels–Alder reactions with dienophiles is reported.

This manuscript presents the synthesis of eight novel noracronycine derivatives containing 1,2,4-triazine moiety and evaluates their anticancer activity in vitro. The obtained compounds exhibit activity in the micromolar range and show selectivity towards glioblastoma A172 and breast cancer Hs578T cells. Compounds incorporating a dihydrotriazine moiety demonstrate an enhanced anticancer profile when compared to a noracronycine derivative lacking a triazine substituent. Furthermore, introducing a pyridyl group into the triazine core increases selective cytotoxicity toward cancerous cells. The lead compound exhibits an IC₅₀ value of 3.4 μM for glioblastoma A172, with a selectivity index of 7.59. Mechanistic studies reveal that the obtained compounds slow down cell division, while no significant apoptosis was detected.

The reaction of pyrazines with 2,5-norbornadiene, an acetylene precursor, as a cascade of Diels–Alder reactions is reported yielding substituted pyridines. In contrast to the known examples of intermolecular Diels–Alder type reaction of pyrazines with acetylene, which usually leads to a mixture of products, in our case the formation of a single isomer was observed. The proposed approach allows the conversion of pyrazines with different types of substitution, except those containing methyl and amino donor groups, to pyridines. In addition, highly functionalized aminonicotic esters were obtained, which can be used for the synthesis of bioactive compounds. An unusual course of the Diels–Alder reaction was found in the case of tetrasubstituted pyrazines, which cleave organic nitriles instead of HCN. Quantum-chemical modeling of possible transition states showed that this Diels–Alder reaction proceeds via cycloaddition of 2,5-norbornadiene to pyrazine with sequential elimination of HCN and cyclopentadiene; the reaction pathway including initial formation of acetylene from norbornadiene and subsequent Diels–Alder reaction with the acetylene was rejected as kinetically unfavorable.

A protocol for C–H/C–H cross-coupling reaction between 7-aminocoumarins and 1,2,4-triazines has been developed. The reaction was carried out under heptafluorobutyric acid catalysis providing products with yield up to 91%. The applicability and scope of the proposed method was demonstrated on 25 compounds containing different substituents both in the triazine ring and at the nitrogen atom of 7-aminocoumarins. The study of the reaction mechanism by EPR and radical trapping suggests that radicals are involved in this transformation.

We have designed and synthesized a series of bioinspired pyrano[2,3-f]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound 4 has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established.

In this work, we report the synthesis of novel coumarin-bipyridine conjugates using a sequence of C–C coupling reaction between 5,7-dimethoxycoumarins and 3-pyridyl-6-aryl-1,2,4-triazines followed by the Boger reaction with norbornandiene to obtain 8-[2,2'-bipyridyl]-5,7-dimethoxycoumarins. Photophysical properties were investigated for the obtained series of 8-[2,2'-bipyridyl]-5,7-dimethoxycoumarins: absorption and emission wavelength maxima are in the region of 212–296 and 401–410 nm, respectively; Stokes shifts are up to 116 nm, and fluorescence quantum yields are up to 15.0%. It was found that titrating the conjugates with Al3+, Zn2+, and Cd2+ ions results in an increase in the intensity of the emission maxima of the complexes, while the opposite effect was observed in the case of titration with Cu2+ ions. These findings suggest that the studied compounds may be considered as promising chemosensing materials. Finally, a positive solvatochromism of 8-[2,2'-bipyridyl]coumarins and their metal complexes was established. The experimental data are supported by mathematical calculations according to the Lippert-Mataga equation and Kosower diagram.

Herein, we report a convenient one-pot synthesis of 1,2,4-triazinyl derivatives of benzocoumarins. The proposed approach consists in the nucleophilic addition of tetrahydrobenzo annulated dimethoxycoumarin to 1,2,4-triazines followed by double oxidation of both dihydrotriazine and tetrahydrobenzo groups with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The nucleophilic addition of the dimethoxycoumarin to 1,2,4-triazines was carried out in the presence of three-fold excess of methanesulfonic acid in DCM at room temperature and take place between positions 4 and 5 of coumarin and 1,2,4-triazine, respectively. The double oxidation step was achieved with 3.6 equivalent of DDQ. Selective oxidation of dihydrotriazine moiety, without affecting the tetrahydrobenzo fragment, was achieved using 1.2 equivalent of tetrachlorobenzoquinone (TCQ). The differences in the oxidation with TCQ and DDQ appear to be related to the higher oxidative potential of DDQ in contrast to TCQ. The advantages of the method are the elimination of the use of transition metals, the availability of starting materials, and the simplicity of the procedure. The proposed approach provides a two-step one-pot protocol for the synthesis of triazinyl benzocoumarins, precursors for the preparation of push-pull pyridinyl chromophore.

A total of 21 novel xanthone and acridone derivatives were synthesized using the reactions of 1,2,4-triazine derivatives with 1-hydroxy-3-methoxy-10-methylacridone, 1,3-dimethoxy-, and 1,3-dihydroxanthone, followed by optional dihydrotiazine ring aromatization. The synthesized compounds were evaluated for their anticancer activity against colorectal cancer HCT116, glioblastoma A-172, breast cancer Hs578T, and human embryonic kidney HEK-293 tumor cell lines. Five compounds (7a, 7e, 9e, 14a, and 14b) displayed good in vitro antiproliferative activities against these cancer cell lines. Compounds 7a and 7e demonstrated low toxicity for normal human embryonic kidney (HEK-293) cells, which determines the possibility of further development of these compounds as anticancer agents. Annexin V assay demonstrated that compound 7e activates apoptotic mechanisms and inhibits proliferation in glioblastoma cells.