Homobivalent Quinazolinimines as Novel Nanomolar Inhibitors of Cholinesterases with Dirigible Selectivity toward Butyrylcholinesterase

Homobivalent dimers of quinazolinimines, which bridge the imine nitrogen atoms via a hepta- and an octamethylene spacer, with different ring sizes of the alicycles were synthesized from the corresponding quinazolinethiones. The resulting compounds show >100-fold increase of inhibitory activities compared to related monomeric compounds yielding low-nanomolar inhibitors. For heptamethylene dimers, mixed inhibition profiles were obtained, whereas for the octamethylene compounds selectivity toward butyrylcholinesterase (>180) can be achieved with an eight-membered alicycle.