title: Tricyclic cyanoguanidines: synthesis, site of action and insecticidal activity of a novel class of reversible acetylcholinesterase inhibitors.
abstract: Bridged-tricyclic cyanoguanidines 1 were found to be active as insecticides. The preparation and structure-activity relationships of oxacyclic (X=O) and carbocyclic (X=CH(2)) analogues of 1 is described. Compounds 1 were found to inhibit acetylcholinesterase with IC(50) 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.
authors.affiliation: DuPont Crop Protection, Stine-Haskell Research Center, PO Box 30, Newark, DE 19714, USA. bruce.l.finkelstein@usa.dupont.com
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Finkelstein
authors.forename: Eric A
authors.initials: EA
authors.lastname: Benner
authors.forename: Maura C
authors.initials: MC
authors.lastname: Hendrixson
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Kranis
authors.forename: James J
authors.initials: JJ
authors.lastname: Rauh
authors.forename: Maya R
authors.initials: MR
authors.lastname: Sethuraman
authors.forename: Stephen F
authors.initials: SF
authors.lastname: McCann
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007313:Insecta / Q000187:drug effects / Q000201:enzymology; D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D006146:Guanidines; D006575:Heterocyclic Compounds, 3-Ring; D007306:Insecticides; D000110:Acetylcholinesterase; C004711:dicyandiamido