The object – reactions of [2+3]-cyclocondensation, Knoevenagel reaction, S-alkylation, aminolysis, polycomponent one-pot chemical processes; the purpose – synthesis of novel derivatives of diclofenac and ibuprofen with fragments of 4-thiazolidinone, oxadiazole and triazole in molecules, its modifications and pharmacological screening of resulted substances; methods – organic synthesis, NMR spectroscopy, chromatographic mass spectrometry, elemental analysis, pharmacological screening, molecular docking; results – methods for the synthesis of 1,2,4-triazole-3-thiol, 1,3,4-oxadiazole-2-thiol, 3H-thiazole, and 4-thiazolidinone derivatives with diclofenac and ibuprofen fragments in molecules as new biologically active substances have been developed. It was found that 1,3,4-oxadiazole-2-thiols and 1,2,4-triazole-3-thiols easily react in the S-alkylation reaction with 2-chloroacetamides based on aromatic amines, 3,5-diarylpyrazolines, 2- aminobenzylthiazoles and 2-amino-4,5-dimethylthiophene and form derivatives previously undescribed in the literature. It was shown for the first time that hydrazides of 2-(4-isobutylphenyl)propionate and 2-(2,6-dichlorophenylamino)phenylacetate acids react readily with thiocarbonyl-bis-thioglycolic acid and form rhodanine derivatives with fragments of the indicated NSAIDs at position 3 of the base heterocycle, and this opens new synthetic routes for chemical modification of 4-thiazolidinone derivatives. An alternative method for the synthesis of 2-(4-isobutylphenyl)-N-(4-oxo-2-thioxothiazolidin-3-yl) -propionamide, based on the acylation of 3-aminorodanine with ibuprofen chloride, has been proposed. It was shown for the first time that hydrazides of {5-[2-(2,6-dichlorophenylamino)-benzyl]-4H-1,2,4-triazol-3-ylsulfanyl}-acetate acids are effective reagents in the design of thiazolidine-triazole hybrid molecules, and it made possible to obtain a new derivative of rhodanine in the reaction with thiocarbonyl-bis-thioglycolic acid and a series of its 5-arylidene derivatives. A systematic approach to the molecular design of 5-aminomethylene-4-thiazolidinones with diclofenac and ibuprofen fragments in position 3 or 5 of the basic core is proposed, based on the interaction of 5-ethoxymethylene-2-[2-(2,6-dichlorophenylamino)phenyl]-N-(4-oxo-2-thioxothiazolidin-3-yl)acetamide with various amines or 5-ethoxymethylene-4-thiazolidinones with hydrazides of 2-(4-isobutylphenyl)propionate and 2-(2,6-dichlorophenylamino) phenylacetic acids. It is shown that N1-acylated 4-ethyl(phenyl) substituted thiosemicarbazides of diclofenac are effective S,N-binucleophiles in [2+3]-cyclocondensations with different equivalents of dielectrophilic synthon [C2]2+ (chloroacetic and 2-bromopropionic acids, α-bromobutyrolactone, ethyl 2-chloroacetoacetate or 2-bromo-1-(4-chlorophenyl)ethanone), which allows to implement an effective synthetic approach to various (4-oxothiazolidin-2-ylidene)- and (3H-thiazol-2-ylidene]-hydrazides of 2-(2,6-dichlorophenylamino)phenylacetic acid. A streamlined synthesis of 152 new heterocyclic compounds was carried out, 2 substances with high antitumor activity, 2 compounds with antitripanosomal action, and 26 derivatives with an anti-inflammatory effect and satisfactory toxicometric parameters were identified. Based on the analysis of the correlation "structure - activity" and docking studies, recommendations for the rational design of potential drugs for the pharmacotherapy of sleeping sickness, cancer and inflammatory processes are proposed; introduced – into educational and scientific processes of Vinnytsya National Pirogov Memorial Medical University, National University of Pharmacy and Zaporizhzhia State Medical University; direction – pharmacy.
