Synthesis, Characterization, and Enzyme Inhibition Properties of 1,2,4-Triazole Bearing Azinane Analogues.

Considering the importance of acetylcholine esterase (AChE, BchE) and α-glucosidase in the treatment of Alzheimer's disease and diabetes mellitus, the synthesis of novel azinane triazole-based derivatives as effective acetylcholinesterase (AchE), α-glucosidase, urease, lipoxygenase (LOX), and butyrylcholinesterase (BChE) inhibitors is described. Azinane analogue () was merged with 1,2,4-triazole to acquire 1-(4-toluenesulfonyl)-4-(3-mercapto-4-methyl-4-1,2,4-triazol-5-yl) piperidine () through a list of intermediates including 1-(4-toluenesulfonyl)-4-(ethoxycarbonyl) piperidine (), 1-(4-toluenesulfonyl)-4-(2-hydrazinocarbonyl)piperidine (), and 1-(4-toluenesulfonyl)-4-[1-(methyl amino thiocarbonyl)-2-hydrazinocarbonyl]piperidine (). The target molecules, 1-(4-toluenesulfonyl)-4-[3-(-alkyl/phenyl/aryl-2-ethanamoyl thio)-4-methyl-4-1,2,4-triazol-5-yl] piperidine (), were achieved through the reaction of with -alkyl/phenyl/aryl-2-bromo ethanamides () as electrophiles. These electrophiles were accomplished by a benign reaction of alkyl/phenyl/aryl amines () and 2-bromo ethanoyl bromide (). The spectral study of IR, 1D-NMR, and EI-MS corroborated the synthesized compounds. Methyl phenyl and methyl phenyl-substituted derivatives and with IC = 0.73 ± 0.54; 36.74 ± 1.24; 19.35 ± 1.28; 0.017 ± 0.53; and 0.038 ± 0.50 μM are found to be the most potent AChE, α-glucosidase, urease, and BChE inhibitors. The high inhibition potential of synthesized molecules against AChE, α-glucosidase, urease, and BChEenzymes inferred their role in enzyme inhibition properties.