Novel Pyrazole Acyl(thio)urea Derivatives Containing
a Biphenyl Scaffold as Potential Succinate Dehydrogenase Inhibitors:
Design, Synthesis, Fungicidal Activity, and SAR
posted on 2024-01-30, 04:12authored byNa-Bo Sun, Li-Jing Min, Xin-Peng Sun, Zhi-Wen Zhai, Joanna Bajsa-Hirschel, Zhe-Cheng Wei, Xue-Wen Hua, Charles L. Cantrell, Hao Xu, Stephen O. Duke, Xing-Hai Liu
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.