Design, synthesis, evaluation and QSAR analysis of N1-substituted norcymserine derivatives as selective butyrylcholinesterase inhibitors

We synthesized a series of N-1-substituted norcymserine derivatives 7a-p and evaluated their anti-cholinesterase activities. In vitro evaluation showed that the pyridinylethyl derivatives 7m-o and the piperidinylethyl derivative 7p improved the anti-butyrylcholinesterase activity by approximately threefold compared to N-1-phenethylnorcymserine (PEC, 2). A quantitative structure-activity relationship (QSAR) study indicated that logS might be a key feature of the improved compounds. (C) 2010 Elsevier Ltd. All rights reserved.