[摘要]：In this study, the authors report the SAR and characterization of two groups of isosorbide-based cholinesterase inhibitors. The first was retention of the 5-nitrate group and introduction of a series of 2-carbamate functionalities. The compds. proved to be potent and selective inhibitors of human plasma butyrylcholinesterase (huBuChE). In the second group, the nitrate ester was removed and replaced with a variety of alkyl and aryl esters. These generally exhibited nanomolar potency with high selectivity for BuChE over acetylcholinesterase (AChE). The most potent and selective compd. was isosorbide-2-benzyl carbamate-5-benzoate with an IC50 of 4.3 nM for BuChE and >50000-fold selectivity over human erythrocyte AChE. Inhibition with these compds. is time-dependent, competitive, and slowly reversible, indicating active site carbamylation.
