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, 1H NMR, and 13C 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 IC50 = 686.4 & PLUSMN; 478.6 & mu;M, eqBChE IC50 = 10.5 & PLUSMN; 5.0 nM, SI = 6.5*104, hBChE IC50 = 32.5 & PLUSMN; 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.

Automated summary

A series of tetrahydrothienopyridine derivatives were designed, synthesized, and evaluated as selective BChE inhibitors. The compounds were analyzed using HRMS, 1H NMR, and 13C NMR. The most potent and selective inhibitor against BChE was found to be 6n.