RESUMO
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.
Assuntos
Lepidópteros/efeitos dos fármacos , Pirimidinonas/química , Pirimidinonas/farmacologia , Receptores Nicotínicos/metabolismo , Animais , Inseticidas/química , Inseticidas/farmacologia , Ligação Proteica/efeitos dos fármacos , Receptores Nicotínicos/química , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Descoberta de Drogas , Inseticidas/farmacologia , Ortópteros/efeitos dos fármacos , Piridinas/farmacologia , Pirimidinonas/farmacologia , Animais , Relação Dose-Resposta a Droga , Inseticidas/química , Estrutura Molecular , Piridinas/química , Pirimidinonas/química , Especificidade da Espécie , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Inseticidas/química , Inseticidas/toxicidade , Antagonistas Nicotínicos/química , Antagonistas Nicotínicos/toxicidade , Pirimidinonas/química , Pirimidinonas/toxicidade , Animais , Hemípteros/efeitos dos fármacos , Hemípteros/fisiologia , Proteínas de Insetos/metabolismo , Lepidópteros/efeitos dos fármacos , Lepidópteros/fisiologia , Receptores Nicotínicos/metabolismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Insetos/efeitos dos fármacos , Inseticidas/química , Oxazolona/química , Aminação , Animais , Insetos/fisiologia , Inseticidas/toxicidade , Oxazolona/toxicidade , Receptores Nicotínicos/metabolismoRESUMO
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.
