The structural modification and biological evaluation of tetrahydrothienopyridine derivatives as selective BChE inhibitors.

A series of tetrahydrothienopyridine derivatives have been designed, synthesized, and evaluated as selective BChE inhibitors. Compounds were analyzed via HRMS, H NMR, and C NMR. The inhibitory effects were evaluated according to the method of Ellman et al. 6n was the most potent and selective inhibitor against BChE (eeAChE IC = 686.4 ± 478.6 μM, eqBChE IC = 10.5 ± 5.0 nM, SI = 6.5*10, hBChE IC = 32.5 ± 6.5 nM). Cell-based assays have confirmed the low neurotoxicity of 6a and 6n and their moderate neuroprotective effects. Compounds 6a and 6n provide novel chemical entities for the treatment of Alzheimer's disease.