SYNTHESIS OF NEW PHARMACOLOGICALLY ORIENTED DERIVATIVES OF 3-NITRO-1,2,4-TRIAZOLES WITH ALICYCLIC SUBSTITUENTS

MFKZFZ

Abstract

1,2,4-Triazole is considered a privileged scaffold with recognized biological and pharmaceutical potential. In addition, due to their physicochemical properties, the use of triazoles is explored in various fields, from medicinal chemistry to materials science. Triazoles have attracted the attention of the scientific community not only with all the above-mentioned properties, but also with their ability to be incorporated into other bioactive and functional molecules. For the synthesis of nitrotriazole derivatives containing cycloalkyl substituents of various structural structures, we studied the patterns of the acid-catalyzed alkylation reaction of 3-nitro-1,2,4-triazole with alicyclic alcohols. The dependences of the ratio of N-substitution products on the reaction time and the nature of the alcohol used were revealed. The prospects for using alicyclic alcohols as alkylating agents are shown. It was found that the interaction of nitrotriazole with cyclopentyl and cyclohexyl alcohols leads to the formation of a mixture of three regioisomeric N1-, N2- and N4-alkylnitrotriazoles. Whereas the introduction of a cycloheptyl substituent by the action of cycloheptanol on 3-nitro-1,2,4-triazole results in the formation of a single reaction product, 1-cycloheptyl-3-nitro-1,2,4-triazole. Such a difference in the composition of the products of the studied reactions is due to the peculiarities of the steric structure of cycloheptanol, which prevent the introduction of a bulky cycloheptyl substituent into the position of the triazole ring adjacent to the nitro group and alkyl group. The structure of the obtained cycloalkylnitrotriazoles was confirmed by a comprehensive study using spectral methods of analysis (¹H, ¹³C NMR and IR spectroscopy). The obtained compounds combine two pharmacophoric fragments in their molecules - a triazole cycle and cycloalkyl substituents of different natures, so one can expect both the manifestation of biological activity characteristic of compounds with these pharmacophoric cycles and the emergence of new useful properties.