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 ( 2 ) was merged with 1,2,4-triazole to acquire 1-(4-toluenesulfonyl)-4-(3-mercapto-4-methyl-4 H -1,2,4-triazol-5-yl) piperidine ( 8 ) through a list of intermediates including 1-(4-toluenesulfonyl)-4-(ethoxycarbonyl) piperidine ( 3 ), 1-(4-toluenesulfonyl)-4-(2-hydrazinocarbonyl)piperidine ( 5 ), and 1-(4-toluenesulfonyl)-4-[1-(methyl amino thiocarbonyl)-2-hydrazinocarbonyl]piperidine ( 7 ). The target molecules, 1-(4-toluenesulfonyl)-4-[3-( N -alkyl/phenyl/aryl-2-ethanamoyl thio)-4-methyl-4 H -1,2,4-triazol-5-yl] piperidine ( 12a-o ), were achieved through the reaction of 8 with N -alkyl/phenyl/aryl-2-bromo ethanamides ( 11a-o ) as electrophiles. These electrophiles were accomplished by a benign reaction of alkyl/phenyl/aryl amines ( 9a-o ) and 2-bromo ethanoyl bromide ( 10 ). The spectral study of IR, 1D-NMR, and EI-MS corroborated the synthesized compounds. Methyl phenyl and methyl phenyl-substituted derivatives 12d and 12m with IC 50 = 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.