Derivatives of oxoisoaporphine alkaloids: A novel class of selective acetylcholinesterase inhibitors

A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a-i Ar-NHCO(CH2)(n)(NRR2)-R-1) and their quaternary methiodide salts (4a-g Ar-NHCO(CH2)(n)N+(CH3)(RRI-)-R-1-I-2) were designed and synthesized as acetyleholinesterase (AChE) or butyr-ylcholinesterase (BuChE) inhibitors. The synthetic compounds exhibited high AChE inhibitory activity with IC50 values in the nanomolar range and high selectivity for AChE over BuChE (45- to 1980-fold). The structure-activity relationships (SARs) were discussed. (c) 2007 Elsevier Ltd. All rights reserved.