Novel acrylamide and methacryloyl carrying piperazine-dihydrofuran derivatives (3a-p) were designed and obtained from radical cyclizations of unsaturated piperazine derivatives (1a-f) with 1,3-dicarbonyl compounds (2a-c) mediated by Mn(OAc)3. Structures of obtained compounds were confirmed with 1 H NMR (proton nuclear magnetic resonance), 13 C NMR (Carbon-13 nuclear magnetic resonance), HRMS (High resolution mass spectrometry), FTIR (Fourier-transform infrared spectroscopy and melting point analysis. Inhibitory activites of all piperazine-dihydrofuran compounds were evaluated against AChE (Acetylcholinesterase) by Ellman method and test results showed that 3a, 3c, 3j and 3l are most active AChEI's (AChE inhibitors) of our work with IC50 (half-maximal inhibitory concentration) values of 2.62, 5.29, 1.17 and 3.90 µM, respectively. Furthermore, ligand-protein interactions and inhibitory activity mechanisms of 3a and 3j were investigated by molecular docking. Finally, in silico molecular property and ADME (absorption, distribution, metabolism and excretion) of potential AChEI's (AChE inhibitor) were predicted by PreADMET and Molinspiration webservers. It can be concluded that the lead compound 3j show excellent inhibiton and satisfactory druglike characteristics.