Synthesis and biological evaluation of new Donepezil-like Thiaindanones as AChE inhibitors

Abstract

Pharmacomodulations of previously reported thiaindanones related to donepezil were achieved with the aim to enhance their AChE inhibitory activity. Condensation of the cyclopentane carbonyl group into hydrazone or cyanolefine derivatives, as well as its hydrogenation and the subsequent substitution of the resulting hydroxyl group led to new 2-(4-benzylpiperazin-1-yl)-N-(1,3-dibromo-6-hydroxy-5,6-dihydro-4H-cyclopenta[c]thien-4-yl) acetamides. The in vitro evaluation of this new series, according to the method of Ellman, shows however that it conserved only partially the biological activity. The best compound remains the alcohol 11 (IC₅₀ = 0.40 μM, against 0.02 μM for donepezil).

• Acetylcholinesterase
• donepezil
• cyclopentathiophene
• thiaindanones
• inhibition

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.