Synthesis and structure-activity relationship study of benzofuran-based chalconoids bearing benzylpyridinium moiety as potent acetylcholinesterase inhibitors.

A series of benzofuran-based chalconoids 6a-v were designed and synthesized as new potential AChE inhibitors. The in vitro assay of synthesized compounds 6a-v showed that most compounds had significant anti-AChE activity at micromolar or sub-micromolar levels. Among the tested compounds, 3-pyridinium derivative 6m bearing N-(2-bromobenzyl) moiety and 7-methoxy substituent on the benzofuran ring exhibited superior activity. This compound with IC₅₀ value of 0.027 μM was as potent as standard drug donepezil.