This study of the interaction system of binucleophilic 3-substituted 4-amino-4H-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4H-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level.

A novel method for synthesizing 1,2,4-triazole- and tetrazole-containing 4H-thiopyrano[2,3-b]quinolines using a new combination of the thio-Michael and aza-Morita–Baylis–Hillman reactions was developed. Target compounds were evaluated for their cytotoxicities and antiviral activities against influenza A/Puerto Rico/8/34 virus in MDCK cells. The compounds showed low toxicity and some exhibited moderate antiviral activity. Molecular docking identified the M2 channel and polymerase basic protein 2 as potential targets. We observed that the antiviral activity of thiopyrano[2,3-b]quinolines is notably affected by both the nature and position of the substituent within the tetrazole ring, as well as the substituent within the benzene moiety of quinoline. These findings contribute to the further search for new antiviral agents against influenza A viruses among derivatives of thiopyrano[2,3-b]quinoline.

Highly purified 5-vinyl-1H-tetrazole was synthesized, which is in great demand in modern medicine and industry as a monomer for obtaining nitrogen-rich macromolecular compounds and a reagent for the complete synthesis of biological compounds. The molecular structure was studied experimentally with sequential X-ray diffraction analysis and theoretically with ab initio quantum chemical calculations. The data from differential scanning calorimetry, nuclear magnetic resonance (¹H, ¹³C, ¹H-¹⁵N, HMBC), high-resolution mass spectrometry and vibrational spectroscopy were analyzed. The results are useful for evaluating the possibility of extending the polymerization of 5-vinyl-1H-tetrazole to synthesize polymers with predictable molecular weight and thermodynamic parameters.

3-(5-Phenyl-2H-tetrazol-2-yl)pyridine was synthesized by treating 5-phenyl-1H-tetrazole with pyridin-3-ylboronic acid under Chan–Evans–Lam coupling conditions. The structure and identity were confirmed by ¹H, ¹³C-NMR spectroscopy, IR spectroscopy, UV–Vis spectroscopy, high-resolution mass spectrometry, and TLC. The molecular structure was studied experimentally by sequential X-ray diffraction analysis and theoretically by DFT B3LYP quantum chemistry calculation.

Introduction. Many compounds containing a tetrazole component are superior in efficacy to other antidiabetic drugs in preclinical studies, and some candidates are already in current trials. The widespread use of tetrazole derivatives to target diabetes-associated targets and therapies that maintain their stability provide the basis for the development of new, effective antidiabetic agents. Aim. A study ( in silico , synthesis, in vivo ) of a series of hybrid 5-phenyltetrazole derivatives was conducted to identify and conduct experimental validation of promising compounds exhibiting hypoglycemic and anti-fat activity. Materials and methods. The synthesis of hybrid heterocyclic compounds was accomplished by acylation of a series of heterocyclic derivatives of N -alkyl-5-aminotetrazole, 4-amino-4 H -1,2,4-triazole-3-thiol, and 2-hydrazinyl-4,6-dimethylpyrimidine with 5-phenyltetrazol-2-ylacetic acid chloride. Results and discussion. As a result of in silico (PASS, docking, scoring) study of biological activity in a series of 5-phenyltetrazole derivatives, the most promising "hybrid" (polynuclear) heterocyclic compounds were identified: N '-(4,6-dimethylpyrimidin-2-yl)-2-(5-phenyl-2 H -tetrazol-2-yl)-acetohydrazide, N -(3-mercapto-4 H -1,2,4-triazol-4-yl)-2-(5-phenyl-2 H -tetrazol-2-yl)-acetamide, N -(1-methyl-1 H -tetrazol-5-yl)-2-(5-phenyl-2 H -tetrazol-2-yl)-acetamide, N -(2-methyl-2 H -tetrazol-5-yl)-2-(5-phenyl-2 H -tetrazol-2-yl)-acetamide and N- tert-butyl-2-({1-[2-(5-phenyl-2 H -tetrazol-2-yl)acetamido]-1 H -tetrazol-5-yl}thio)acetamide. These predictions are of interest as potential computer-aided means for the pharmacological correction of various metabolic phenomena. A rational method for synthesizing these compounds was developed and implemented, the structure and individuality of which were demonstrated using modern instrumental physicochemical methods. In vivo studies demonstrated that these heterocyclic compounds exhibit hypoglycemic and pronounced anti-lipid activity. Conclusion. The study of hybrid 5-phenyltetrazole derivatives revealed pronounced hypoglycemic activity. It was found that the anti-lipid activity in this case is not directly related to the hypoglycemic effect, unlike the manifestation characteristic of the sensitizer metformin.