SYNTHESIS AND PROPERTIES OF 8-BENZYLYDENEHYDRAZINYLSUBSTITUTED 1-BUTYL-3-METHYL-7-(THIETAN-3-YL)-3,7-DIHYDRO-1HPURINE-2,6-DIONES

Objective: synthesis of new 8-benzylydenehydrazinyl-substituted 1-butyl-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones as promising biologically active substances.

Material and methods. Target 8-benzylydenehydrazinyl-substituted 7-(thietan-3-yl)-, 7-(1-oxothietan-3-yl)- and 7-(1,1-dioxothietan-3-yl)-1-butyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones were obtained from the corresponding 8-bromo-3,7-dihydro-1H-purine-2,6-diones in two steps. First, 8-hydrazinyl-substituted purine-2,6-diones were synthesized by interaction with hydrazine hydrate. Then condensation with 5-bromo-2-hydroxybenzaldehyde and 4-(dimethylamino) benzaldehyde gave the corresponding 8-benzylydenehydrazinyl-substituted 7-(thietan-3-yl)-, 7-(1-oxothietan-3-yl)- and 7-(1,1-dioxothietan-3-yl)-1-butyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones with 71-94% yield. The structure of the synthesized compounds was confirmed by GC/MS, UV, IR, and 1H NMR spectra. When determining the antimicrobial activity, it was found that the test compounds exhibit mild antimicrobial properties (the minimum inhibitory concentration is more than 100 mg/ml). Calculation of physicochemical descriptors, prediction of parameters of adsorption, distribution, metabolism, excretion, pharmacokinetic properties, and toxicity of the synthesized compounds in silico using the SwissADME and pkCSM websites were carried out.

Results and conclusions. New 8-benzylydenehydrazinyl-substituted 1-butyl-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones were synthesized in good yields, their antimicrobial properties were studied. A weak antimicrobial effect indicates the need for modification of the structure to achieve the required pharmacological activity. The results of in silico prediction can be used in the further study of 8-benzylydenehydrazinyl-substituted 1-alkyl-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones as potential biologically active connections.

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