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The aim of this study is the direct synthesis of new (4,6-dimethylpyrimidin-2-yl)thio-N-acetamides derivatives as possible anticonvulsants. The interaction of thiourea with acetylacetone in sodium ethoxide resulted in the scaffold of 4,6-dimethyl-2-thiopyrimidine. Thioacetamide derivatives were synthesized by alkylation of 4,6-dimethyl-2thiopyrimidine with comparable α-chloroacetamides in the Dimethylformamide (DMF) environment and in the presence of К 2 СО 3. The methods of 1 H and 13 C Nuclear magnetic resonance (NMR) spectroscopy, Liquid chromatographymass spectrometry (LS/MS), and elemental analysis established the structure of the synthesized compounds. The affinity of the studied compounds with anticonvulsant biotargets-Type-A γ-aminobutyric acid receptor (GABAAR) and the gamma-aminobutyric acid-aminotransferase enzyme-was carried out using the molecular-docking method. The highest affinity was predicted for the compound having 4-bromophenyl substituent: −7.0 (GABAA) and −8.0 (GABAАТ) kcal/mol. Nevertheless, all the studied compounds conceded to the reference ligands-phenobarbital (−7.6 kcal/mol) and vigabatrin (−9.0 kcal/mol). The model of pentylenetetrazole-induced seizures in rats has shown that the studied compounds have moderate anticonvulsant activity. 4-Bromophenyl acetamide has also shown the most pronounced activity: the substance statistically significantly extended the latency period and reduced the duration of seizures by 3.4 and 2.2 times, respectively; moreover, it reduced lethality of the laboratory animals by 80% and by 2.5 times severity of seizures. Correspondence between the docking results and in vivo studies, using PTZ-induced seizures, as well as some parameters of "structure-anticonvulsant activity" correlation, was determined.

According to the World Journal of Gastroenterology, more than 5 million people worldwide suffer from inflammatory bowel disease. The use of phytotherapeutic remedies in treatment of chronic inflammatory processes can be an effective alternative in patient’s therapy. The advantage of herbal medicines is the ability to influence various links of pathogenesis, lack of addiction, and the absence of withdrawal syndrome with long-term use in chronic pathology. In order to develop a new combined remedy with anti-inflammatory activity for the treatment of colitis, thirteen herbs, which are used in official or traditional medicine in inflammatory processes, were selected among the Ukrainian flora members. To select the most promising drugs and optimize further pharmacological research, molecular docking of the main active substances of the selected herbs to the fundamental pro-inflammatory enzymes – lipoxygenase-5 (LOX-5) and cyclooxygenase-2 (COX-2) – was carried out. Native inhibitors AKBA and celecoxib, respectively, were used as the reference ligands. The selection of candidate structures for in silico research was carried out according to the bibliosemantic research and logical-structural analysis concerning anti-inflammatory effect of the substances, which are part of chemical composition of the selected herbs. Molecular docking results have shown a high affinity level for the active site of the LOX-5 inhibitor gallotannin, quercetin, inulin, sitosterine, and moderate for ellagic acid. High affinity level for the active site of the COX-2 inhibitor was found for inulin, quercetin, gallotannin, ellagic acid and urticin A, moderate one – for gallic acid. For the further pharmacological in vitro and in vivo studies for anti-inflammatory activity, medicinal herbs with the highest content of the mentioned compounds were selected: Inula helenium, Cichorium intybus, Capsella bursa-pastoris, Foeniculum vulgare, Equisetum arvense, Veronica officinalis. Besides, it is recommended to use aqueous extracts of the selected herbs for the further pharmacological studies.

The rapid development in bacterial resistance to many groups of known antibiotics forces the researchers to discover antibacterial drug candidates with previously unknown mechanisms of action, one of the most relevant being the inhibition of tRNA (Guanine37-N1)-methyltransferase (TrmD). The discovery of selective TrmD inhibitors in the series of carboxamide derivatives of thienopyrimidines became a background for further modification of the similar structures aimed at the development of promising antibacterial agents. As part of this research, we carried out the construction of heterocyclic hybrids bearing the moieties of thieno[2,3-d]pyrimidine and benzimidazole starting from 3,5-dimethyl-4-oxo-2-thioxo-1H-thieno[2,3-d]pyrimidine-6-carboxylic acid, which was used as the pivotal intermediate. The hybrid molecule of 6-(1H-benzimidazol-2-yl)-3,5-dimethyl-2-thioxo-1H-thieno[2,3-d]pyrimidin-4-one prepared via condensation of the carboxylic acid with ortho-phenylenediamine was further alkylated with aryl/hetaryl chloroacetamides and benzyl chloride to produce the series of S-alkyl derivatives. The results of molecular docking studies for the obtained series of S-alkyl benzimidazole-thienopyrimidines showed their high affinity to the TrmD isolated from the P. aeruginosa. The results of antimicrobial activity screening revealed the antimicrobial properties for all of the studied molecules against both Gram-positive and Gram-negative bacteria and the Candida albicans fungal strain. The highest antimicrobial activity was determined for 2-{[6-(1H-benzimidazol-2-yl)-3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl]thio}-N-(4-isopropylphenyl)acetamide, which also had the highest affinity to the TrmD inhibitor’s binding site according to the docking studies results.

6-Heteryl-5-methylthieno[2,3-d]pyrimidin-2,4(1H,3H)-diones are of great interest as the promising objects for the search of antibacterials. In this communication, we obtained 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione by interaction of 6-(bromoacetyl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione with 2-aminopyridine. The obtained heterocyclic hybrid was further modified by alkylation with 2-chloroarylacetamides. Antimicrobial activity studies for the synthesized compounds using the agar well diffusion method revealed their moderate activity against S. aureus, E. coli and B. subtilis. According to the double dilution assay MIC value results for 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneagainst P. aeruginosa was less than the value determined for the reference drug streptomycin. The docking study of the synthesized compounds to the active site of TrmD isolated from P. aeruginosa did not show their effective inhibitory activity.