Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross-linker are investigated in acetyl- and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3-(3,4-Dichlorophenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50=0.27 mu m). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed-type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks beta -amyloid (A beta) self-aggregation with a ratio of 44.11% at 100 mu m and significantly protects PC12 cells from H2O2-damage in a dose-dependent manner.