Introduction: 3-(2-butyl-5-chloro-1H-imidazole-4-yl)-N-[4-methoxy-3-(trifluoromethyl)phenyl]-4,5-dihydro-1,2-oxazole-5-carboxamide is new antirheumatic drug. It is necessary to identify and synthesize the biotransformation products for its complete pharmacokinetic study. Materials and Methods: A biotransformation study was carried out by intraperitoneal administration of the drug to Wistar rats and Soviet Chinchilla breed rabbits. Animal blood sampling was performed before the injection and 0.5 h, 1 h, 2 h, 4 h, 24 h after the injection of the investigated compound. The samples were immediately centrifuged for plasma separation. Urine was simultaneously collected from rats before the administration and at intervals of 0-2 h, 2-4 h, 4-6 h, 6-24 h after administration, faeces – before administration and at intervals of 0-12 h and 12-24 h after administration. The samples were analyzed by HPLC-MS/MS after immediate preparation by adding acetonitrile. Results and Discussion: 3-(2-butyl-5-chloro-1H-imidazole-4-yl)-4,5-dihydro-1,2-oxazole-5-carboxylic acid and 4-methoxy-3-(trifluoromethyl)aniline – hydrolysis products of the active substance were found during the analysis of plasma, urine and fecal samples. The 4,5-dihydro-1,2-oxazole-5-carboxylic acid derivative has been synthesized. The second metabolite is a raw material for production of active pharmaceutical substance. During comparative tests, no significant difference between the retention times, ratio areas of chromatographic peaks at the main MRM-transitions and mass spectra of these metabolites on chromatograms of standard and animal samples was found, which indicates the correct identification of biotransformation products. Conclusion: The studied drug undergoes biotransformation by hydrolysis to form two main metabolites: 3-(2-butyl-5-chloro-1H-imidazole-4-yl)-4,5-dihydro-1,2-oxazole-5-carboxylic acid and 4-methoxy-3-(trifluoromethyl)aniline. The structure of the metabolites was confirmed by comparison with the synthesized standard samples using HPLC-MS/MS.

A preparative procedure has been developed for the synthesis of a series of new medicinally relevant 3-aryl-5-(aryloxymethyl)-1,2,4-oxadiazoles in 46–66% yields by alkylation of substituted phenols with 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in the system K₂CO₃/KI/DMF. Poorly studied 3-R-4H-1,2,4-oxadiazin-5(6H)-ones were synthesized by a new method based on the reaction of methyl chloroacetate with amidoximes in the superbasic system t-BuONa/DMSO. The synthesized compounds at concentrations of up to 250 μg/mL showed no antibacterial activity against sensitive strains of Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas fluorescens, which supposedly suggests their low toxicity for human intestinal and mucous microflora.

Methods were developed for the synthesis of a series of new thioethers, interesting for medical chemistry, by reacting 4-fluorothiophenol, 2-mercaptobenzoxazole and 5-methoxy-2-mercaptobenzimidazole with 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles. The conditions for the oxidation of the obtained thioethers into the corresponding sulfones were selected. Analysis of the results of screening of the prepared derivatives against sensitive strains of Escherichia coli, Pseudomonas fluorescens, Staphylococcus aureus, Bacillus cereus and Candida albicans showed the presence of high and moderate antibacterial activity in a number of compounds in drug concentrations up to 250 μg/mL.