Tricyclic cyanoguanidines: synthesis, site of action and insecticidal activity of a novel class of reversible acetylcholinesterase inhibitors Original Research Article

Bridged-tricyclic cyanoguanidines 1 were found to be active as insecticides. The preparation and structure–activity relationships of oxacyclic (X=O) and carbocyclic (X=CH2) analogues of 1 is described. Compounds 1 were found to inhibit acetylcholinesterase with IC50 values comparable to the organophosphate Paraoxon. Unlike organophosphates, cyanoguanidines 1 were shown to reversibly bind acetylcholinesterase. This mode of action is shared by the structurally-related natural product Huperzine A.