Design, Synthesis, and Biological Evaluation of 1,3,4-Oxadiazole Derivatives

A series of 1,3,4-oxadiazole derivatives were synthesized starting from substituted phenylacetic acids, and their structures were confirmed by IR, NMR, and HRMS data. The synthesized compounds showed potent in vitro cholinesterase inhibitory activities with IC 50 values of 8.59 μM against butyrylcholinesterase ( 6a ) and 7.12 μM against acetylcholinesterase ( 6f ). Molecular docking studies indicated that compound 6f could interact with the peripheral anion that binds to acetylcholinesterase. Moreover, compound 6c also exhibited strong anti-inflammatory effect. This compound could significantly reduce LPS-induced secretion of inflam­matory cytokines IL-6, IL-1β, and TNF-α in RAW 264.7 cells. These results suggested that 1,3,4-oxadiazole derivatives may be promising lead compounds for the treatment of Alzheimer’s disease.