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Discovery of Highly Selective and Nanomolar Carbamate-Based Butyrylcholinesterase Inhibitors by Rational Investigation into Their Inhibition Mode

Sawatzky, Edgar ; Wehle, Sarah ; Kling, Beata ; Wendrich, Jan ; Bringmann, Gerhard ; Sotriffer, Christoph A. ; Heilmann, Jörg ; Decker, Michael



Abstract

Butyrylcholinesterase (BChE) is a promising target for the treatment of later stage cognitive decline in Alzheimer's disease. A set of pseudo-irreversible BChE inhibitors with high selectivity over hAChE was synthesized based on carbamates attached to tetrahydroquinazoline scaffolds with the 2-thiophenyl compound 2p as the most potent inhibitor of eqBChE (K-C = 14.3 nM) and also of hBChE (K-C = ...

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