RESUMEN
As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, a series of new pyrazole acyl(thio)urea compounds containing a diphenyl motif were designed and synthesized. Their structures were confirmed by 1H NMR, HRMS, and single X-ray crystal diffraction analysis. Most of these compounds possessed excellent activity against 10 fungal plant pathogens at 50 µg mL-1, especially against Rhizoctonia solani, Alternaria solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Cercospora arachidicola. Interestingly, compounds 3-(difluoromethyl)-1-methyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9b, EC50 = 0.97 ± 0.18 µg mL-1), 1,3-dimethyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9a, EC50 = 2.63 ± 0.41 µg mL-1), and N-((4'-chloro-[1,1'-biphenyl]-2-yl)carbamoyl)-1,3-dimethyl-1H-pyrazole-4-carboxamide (9g, EC50 = 1.31 ± 0.15 µg mL-1) exhibited activities against S. sclerotiorum that were better than the commercial fungicide bixafen (EC50 = 9.15 ± 0.05 µg mL-1) and similar to the positive control fluxapyroxad (EC50 = 0.71 ± 0.11 µg mL-1). These compounds were not significantly phytotoxic to monocotyledonous and dicotyledonous plants. Structure-activity relationships (SAR) are discussed by substituent effects/molecular docking, and density functional theory analysis indicated that these compounds are succinate dehydrogenase inhibitors.
Asunto(s)
Compuestos de Bifenilo , Fungicidas Industriales , Succinato Deshidrogenasa , Urea , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Fungicidas Industriales/química , Pirazoles/química , Antifúngicos/farmacologíaRESUMEN
BACKGROUND: In recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure-activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity. RESULTS: Twenty-seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L-1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 µg mL-1 . In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method. CONCLUSION: It is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry.
Asunto(s)
Ascomicetos/efectos de los fármacos , Fungicidas Industriales/farmacología , Hongos Mitospóricos/efectos de los fármacos , Phytophthora infestans/efectos de los fármacos , Pirazoles/farmacología , Fungicidas Industriales/síntesis química , Fungicidas Industriales/química , Pirazoles/síntesis química , Pirazoles/química , Relación Estructura-ActividadRESUMEN
A series of novel 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one derivatives were synthesized and identified by (1)H NMR, single crystal X-ray diffraction, elemental analysis or HRMS, and their herbicidal activities were determined at different concentrations. It was found that some of the title compounds possess high herbicidal activity. Furthermore, DFT calculation was used to study the SAR.