Neuroprotective Tri- and Tetracyclic BChE Inhibitors Releasing Reversible Inhibitors upon Carbamate Transfer

摘要: Tri- and tetracyclic nitrogen-bridgehead compounds were designed synthesized to yield micromolar cholinesterase (ChE) inhibitors. Structure–activity relationships identified potent with butyrylcholinesterase selectivity. These selected as starting points for the design synthesis of carbamate-based (pseudo)irreversible Compounds superior inhibitory activity selectivity obtained kinetically characterized also regard velocity enzyme carbamoylation. Structural elements introduced that additionally showed neuroprotective properties on a hippocampal neuronal cell line (HT-22) after glutamate-induced intracellular reactive oxygen species generation. We have selective pseudoirreversible inhibitors release reversible carbamate transfer active site cholinesterases.