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A series of new thiophene derivatives has been synthesized using the Gewald protocol. The acetylcholinesterase inhibition activity was assayed according to Ellman’s method using donepezil as reference. Some of the compounds were found to be more potent inhibitors than the reference. 2-(2-(4-(4-Methoxyphenyl)piperazin-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[<em>b</em>]thiophene-3-carboxamide (<strong>IIId</strong>) showed 60% inhibition, compared to only 40% inhibition by donepezil.