Synthesis of novel 1,2,3-triazole-based hybrids via click reactions

Abstract

1,2,3-Triazoles have attracted the interest of researchers due to their wide range of biological activities which include antitumor, anti-leishmanial, bioluminescent and fungicidal activities This paper describes the synthesis of novel triazole hybrids containing biologically active fragments through cycloaddition (click) reactions, with the aim of increasing the diversity of known and active 1,2,3-triazole derivatives. All new compounds have been characterized by physicochemical methods.

New Bicyclic Pyridine-Based Hybrids Linked to the 1,2,3-Triazole Unit: Synthesis via Click Reaction and Evaluation of Neurotropic Activity and Molecular Docking

“…However, the spectroscopic data (IR, NMR spectra, and X-ray data) strongly evidenced that pyrano [3,4- c ]pyridines 1 in the crystalline state and in solution exist only in the lactam (NH) tautomeric form [ 26 ]. Interestingly, in alkaline solution the situation changes, where by the alkylation of condensed pyridines 1 in basic conditions we obtained high yields of O -alkylated derivatives [ 24 , 28 ]. The same situation was observed during the reaction of compound 1 with propargyl bromide.…”

“…The same situation was observed during the reaction of compound 1 with propargyl bromide. As a result, relevant O -alkylated derivatives 2a – i [ 24 ] were obtained under basic conditions at room temperature in high yields ( Scheme 1 , Table 1 ).…”

“…In order to obtain the second component, namely azides, we started with 6-piperazino derivatives of pyrano [3,4-c]pyridines 4a – c [ 15 ]. Thus, by acylation of compound 4 with chloroacetyl chloride, the relevant 1(8)-alkyl-3(6)-[4-(chloroacetyl)piperazin-1-yl]pyridine-4(5)-carbonitriles 5a – c [ 24 ] were obtained. Further reaction of compound 5 with sodium azide in acetone led to the formation of 1(8)-alkyl-3(6)-[4-(azidoacetyl)piperazin-1-yl][ c ]pyridine-4(5)-carbonitriles 6a – c [ 24 ] in high yields ( Scheme 2 ).…”

“…The synthesis of new bioactive hybrids was carried out according to the proposed general Scheme 3 via reactions between the propargylated compounds 2 and azido derivatives 6 under the Cu-catalyzed azide-alkyne click reaction [ 24 ]. In the majority of the reactions, the hybrids 7a – u were obtained in high yields (Y = 72–87%; Table 3 ).…”

“…Taking into account the above-mentioned results, herein we describe the synthesis of new original hybrid compounds as potential biologically active substances while studying their neurotropic properties. The click chemistry [ 21 , 22 , 23 , 24 ] was used to synthesize the corresponding terminal triple bond and azido group based on the biologically active bicyclic pyridine derivatives.…”