ABSTRACT
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program that led to the identification of dicloromezotiaz as a potent insecticide to control a broad range of lepidoptera. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.
Subject(s)
Lepidoptera/drug effects , Pyrimidinones/chemistry , Pyrimidinones/pharmacology , Receptors, Nicotinic/metabolism , Animals , Insecticides/chemistry , Insecticides/pharmacology , Protein Binding/drug effects , Receptors, Nicotinic/chemistry , Structure-Activity RelationshipABSTRACT
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program which led to the discovery of triflumezopyrim as a highly potent insecticide controlling various hopper species. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.
Subject(s)
Drug Discovery , Insecticides/pharmacology , Orthoptera/drug effects , Pyridines/pharmacology , Pyrimidinones/pharmacology , Animals , Dose-Response Relationship, Drug , Insecticides/chemistry , Molecular Structure , Pyridines/chemistry , Pyrimidinones/chemistry , Species Specificity , Structure-Activity RelationshipABSTRACT
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we report the discovery, evolution, and preparation of this class of chemistry. Our efforts in structure-activity relationship elucidation and biological activity evaluation are also presented.
Subject(s)
Insecticides/chemistry , Insecticides/toxicity , Nicotinic Antagonists/chemistry , Nicotinic Antagonists/toxicity , Pyrimidinones/chemistry , Pyrimidinones/toxicity , Animals , Hemiptera/drug effects , Hemiptera/physiology , Insect Proteins/metabolism , Lepidoptera/drug effects , Lepidoptera/physiology , Receptors, Nicotinic/metabolism , Structure-Activity RelationshipABSTRACT
N-Substituted amino-2(5H)-oxazolones A are a novel class of insecticides acting as nicotinic acetylcholine receptor (nAChR) agonists and show potent activity against hemipteran insect species. Here we report the discovery and preparation of this class of chemistry. Our efforts in SAR elucidation, biological activity evaluation, as well as mode-of-action studies are also presented.
Subject(s)
Insecta/drug effects , Insecticides/chemistry , Oxazolone/chemistry , Amination , Animals , Insecta/physiology , Insecticides/toxicity , Oxazolone/toxicity , Receptors, Nicotinic/metabolismABSTRACT
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.
