Annulated bicyclic isothioureas: identification of active and selective butyrylcholinesterase inhibitors

Structural optimization of butyrylcholinesterase inhibitors, 5-bromomethyl- and 5-iodomethyl-N,N-disubstituted 2-aminothiazolines, led to a series of their annulated bicyclic analogues, obtained by intramolecular cyclization of cycloalkenylthioureas. The most active compound in this series, cyclohepta[d]thiazol-2-amine, is a mixed-type butyryl-cholinesterase inhibitor with IC₅₀ = 130 nm, highly selective compared to acetylcholinesterase and non-toxic at 100 μm concentrations.