RESUMO
Fluazaindolizine is a new highly effective and selective product for the control of plant parasitic nematodes. Specificity for nematodes coupled with absence of activity against the target sites of commercial nematicides suggests that fluazaindolizine has a novel mode of action. The discovery, structure-activity development and biological properties for this new class of nematicides are presented.
Assuntos
Compostos Heterocíclicos com 2 Anéis/farmacologia , Indolizinas/farmacologia , Praguicidas/farmacologia , Sulfonamidas/farmacologia , Animais , Caenorhabditis elegans/efeitos dos fármacos , Produtos Agrícolas/parasitologia , Drosophila melanogaster/efeitos dos fármacos , Compostos Heterocíclicos com 2 Anéis/síntese química , Compostos Heterocíclicos com 2 Anéis/toxicidade , Indolizinas/síntese química , Indolizinas/toxicidade , Praguicidas/síntese química , Praguicidas/toxicidade , Raízes de Plantas/parasitologia , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/toxicidade , Tylenchoidea/efeitos dos fármacosRESUMO
Isoxazoline insecticides have been shown to be potent blockers of insect GABA receptors with excellent activity on a broad pest range, including Lepidoptera and Hemiptera. Herein we report on the synthesis, biological activity and mode-of-action for a class of 4-heterocyclic aryl isoxazoline insecticides.
Assuntos
Canais de Cloreto/antagonistas & inibidores , Inseticidas/farmacologia , Isoxazóis/farmacologia , Receptores de GABA/metabolismo , Animais , Canais de Cloreto/metabolismo , Relação Dose-Resposta a Droga , Insetos , Inseticidas/síntese química , Inseticidas/química , Isoxazóis/síntese química , Isoxazóis/química , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
A series of highly active fluorinated anthranilic diamide insecticides have been prepared and their biological activity assessed on two aphid species in the search for systemically active compounds that control Hemiptera. In addition, we have demonstrated a new synthesis of N-aryl 3-fluoropyrazoles.
Assuntos
Afídeos/efeitos dos fármacos , Inseticidas/síntese química , ortoaminobenzoatos/química , ortoaminobenzoatos/farmacologia , Amidas/química , Amidas/farmacologia , Animais , Halogenação , Hemípteros/efeitos dos fármacos , PirazóisRESUMO
Rynaxypyr is a highly potent and selective activator of insect ryanodine receptors with exceptional activity on a broad range of Lepidoptera. A strong correlation between insecticidal activity and ryanodine receptor activation is observed along with selective activity against insect over mammalian receptors. The synthesis and biological results are presented.
Assuntos
Inseticidas/farmacologia , Lepidópteros/efeitos dos fármacos , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , Animais , Linhagem Celular , Humanos , Inseticidas/síntese química , Inseticidas/química , Lepidópteros/citologia , Camundongos , Estrutura Molecular , Ratos , Relação Estrutura-Atividade , Testes de Toxicidade Aguda , Regulação para Cima/efeitos dos fármacos , ortoaminobenzoatos/síntese química , ortoaminobenzoatos/químicaRESUMO
A novel class of anthranilic diamides has been discovered with exceptional insecticidal activity on a range of Lepidoptera. These compounds have been found to exhibit their action by release of intracellular Ca2+ stores mediated by the ryanodine receptor. The discovery, synthesis, structure-activity, and biological results are presented.
Assuntos
Inseticidas/química , Inseticidas/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , ortoaminobenzoatos/química , ortoaminobenzoatos/farmacologia , Aminação , Animais , Cálcio/metabolismo , Insetos/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , ortoaminobenzoatos/classificaçãoRESUMO
BACKGROUND AND AIMS: Antibodies directed against the porin protein C of Escherichia coli (anti-OmpC) and Pseudomonas fluorescens (anti-I2) have recently been described in Crohn's disease (CD). Those directed against Saccharomyces cerevisiae (ASCA) and the perinuclear component of neutrophils (pANCA) have been more widely studied and may be of diagnostic importance. We aimed to assess the frequency of anti-OmpC, anti-I2, ASCA, and pANCA, in an independent Scottish CD cohort, establish phenotypic associations, and compare with a U.S. cohort. METHODS: One hundred and forty-two well-characterized CD patients (76 females, median age 39 yr (17-88)) were studied. CD was classified by the Vienna classification. Sera were assayed for anti-OmpC, anti-I2, ASCA, and pANCA. Allele specific primers were used for NOD2/CARD15 genotyping. RESULTS: Anti-OmpC, anti-I2, ASCA, and pANCA were present in sera from 37%, 52%, 39%, and 14% of CD patients, respectively. Multivariate analysis demonstrated independent associations of anti-OmpC to be progression of disease type (p= 0.005) and long disease duration (p= 0.002), and those of anti-I2 to be long disease duration (p= 0.002) and the need for surgery (p= 0.033). ASCA were associated with disease progression (p < 0.001). When the presence and magnitude of all antibody responses were considered, reactivity to microbial components was associated with long disease duration (p < 0.001), progression of disease type (p < 0.001), penetrating disease (p= 0.008), small bowel disease (p < 0.02), and the need for surgery (p < 0.001). There was no association of antibody status to NOD2/CARD15 genotype. CONCLUSION: Reactivity to microbial components is associated with severe CD characterized by small bowel involvement, frequent disease progression, longer disease duration, and greater need for intestinal surgery.