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

Abstract

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 ± 478.6 μM, eqBChE IC₅₀ = 10.5 ± 5.0 nM, SI = 6.5*10⁴, hBChE IC₅₀ = 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.

Keywords: Alzheimer's disease; BChE inhibitor; Tetrahydrothienopyridine.