Abstract
Background: In recent years, pyrazole carboxamide derivatives possessed excellent fungicidal activity. In the process of designing new fungicides, the carboxamide group was modified in order to find novel structure pyrazole carboxamide derivatives.
Methods: Ten novel trifluoromethyl pyrazole acyl thiourea derivatives were designed and synthesized. In vivo fungicidal activities of these compounds were tested against Fusarium oxysporum, Corynespora mazei and Botrytis cinerea, respectively.
Results: Particularly compounds exhibited significant control effective at 100 mg/L. More importantly, some compounds showed the good control effective at 10 mg/L. Furthermore, docking was established to study the structure-activity relationship of the title compounds.
Conclusion: It is possible that trifluoromethylpyrazole acyl thiurea derivatives, which possess good control effective against Botrytis cinerea, may become novel lead compounds for the development of fungicides with further structure modification.
Keywords: Trifluoromethylpyrazole, thiourea, antifungal activity, docking, fusarium oxysporum, corynespora mazei, botrytis cinerea.
Graphical Abstract
[2]
Gobeil-Richard, M.; Tremblay, D.M.; Beaulieu, C.; Van der Heyden, H.; Carisse, O. A pyrosequencing-based method to quantify genetic substitutions associated with resistance to succinate dehydrogenase inhibitor fungicides in Botrytis spp. Populations. Pest Manag. Sci., 2016, 72, 566-573.
[3]
Hidalgo, W.; Cano, M.; Arbelaez, M.; Zarrazola, E.; Gil, J.; Schneider, B.; Otalvaro, F. 4-Phenylphenalenones as a template for new photodynamic compounds against Mycosphaerella fijiensis. Pest Manag. Sci., 2016, 72, 796-800.
[4]
Dooley, H.; Shaw, M.W.; Spink, J.; Kildea, S. The effect of succinate dehydrogenase inhibitor/azole mixtures on selection of Zymoseptoria tritici isolates with reduced sensitivity. Pest Manag. Sci., 2016, 72, 1150-1159.
[5]
Ye, Y.H.; Ma, L.; Dai, Z.C.; Xiao, Y.; Zhang, Y.Y.; Li, D.D.; Wang, J.X.; Zhu, H.L. Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors. J. Agric. Food Chem., 2014, 62, 4063-4071.
[6]
Mu, J-X.; Shi, Y-X.; Yang, M-Y.; Sun, Z-H.; Liu, X-H.; Li, B-J.; Sun, N-B. Design, synthesis, DFT study and antifungal activity of pyrazolecarboxamide derivatives. Molecules, 2016, 21, 68.
[7]
Du, S.; Tian, Z.; Yang, D.; Li, X.; Li, H.; Jia, C.; Che, C.; Wang, M.; Qin, Z. Synthesis, antifungal activity and structure-activity relationships of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides. Molecules, 2015, 20, 8395-8408.
[8]
Liu, X.H.; Xu, X.Y.; Tan, C.X.; Weng, J.Q.; Xin, J.H.; Chen, J. Synthesis, crystal structure, herbicidal activities and 3D-QSAR study of some novel 1,2,4-triazolo [4,3-a]pyridine derivatives. Pest Manag. Sci., 2015, 71, 292-301.
[9]
Liu, X.H.; Zhai, Z.W.; Xu, X.Y.; Yang, M.Y.; Sun, Z.H.; Weng, J.Q.; Tan, C.X.; Chen, J. Facile and efficient synthesis and herbicidal activity determination of novel 1,2,4-triazolo [4,3-a]pyridin-3(2H)-one derivatives via microwave irradiation. Bioorg. Med. Chem. Lett., 2015, 25, 5524-5528.
[10]
Zhang, L.J.; Yang, M.Y.; Sun, Z.H.; Tan, C.X.; Weng, J.Q.; Wu, H.K.; Liu, X.H. Synthesis and antifungal activity of 1,3,4-thiadiazole derivatives containing pyridine group. Lett. Drug Des. Discov., 2014, 11, 1107-1111.
[11]
Liu, X.H.; Weng, J.Q.; Wang, B.L.; Li, Y.H.; Tan, C.X.; Li, Z.M. Microwave-assisted synthesis of novel fluorinated 1,2,4-triazole derivatives, and study of their biological activity. Res. Chem. Intermed., 2014, 40, 2605-2612.
[12]
Zhai, Z.W.; Yang, M.Y.; Sun, Z.H.; Liu, X.H.; Weng, J.Q.; Tan, C.X. Facile and efficient synthesis of novel 1,2,3-thiadiazole derivatives using microwave irradiation. J. Chem. Res., 2015, 39, 340-342.
[14]
Liu, X.H.; Sun, Z.H.; Yang, M.Y.; Tan, C.X.; Weng, J.Q.; Zhang, Y.G.; Ma, Y. Microwave assistant one pot synthesis, crystal structure, antifungal activities and 3D-QSAR of novel 1,2,4-triazolo [4,3-a]pyridines. Chem. Biol. Drug Des., 2014, 84, 342-347.
[15]
Liu, X.H.; Fang, Y.M.; Xie, F.; Zhang, R.R.; Shen, Z.H.; Tan, C.X.; Weng, J.Q.; Xu, T.M.; Huang, H.Y. Synthesis and in vivo fungicidal activity of some new quinoline derivatives against rice blast. Pest Manag. Sci., 2017, 73, 1900-1907.
[16]
Yan, S.L.; Yang, M.Y.; Sun, Z.H.; Min, L.J.; Tan, C.X.; Weng, J.Q.; Wu, H.K.; Liu, X.H. Synthesis and antifungal activity of 1,2,3-thiadiazole derivatives containing 1,3,4-thiadiazole moiety. Lett. Drug Des. Discov., 2014, 11, 940-943.
[17]
Cheng, L.; Zhang, R.R.; Wu, H.K.; Xu, T.M.; Liu, X.H. The synthesis
of 6-(tert-butyl)-8-fluoro-2,3-dimethylquinoline carbonate
derivatives and their antifungal activity against pyricularia oryzae. Front. Chem. Sci. Eng, 2018.
[http://dx.doi.org/10.1007/s11705-018-1734-7]
[http://dx.doi.org/10.1007/s11705-018-1734-7]
[18]
Zhai, Z.W.; Shi, Y.X.; Yang, M.Y.; Zhao, W.; Sun, Z.H.; Weng, J.Q.; Tan, C.X.; Liu, X.H.; Li, B.J.; Zhang, Y.G. Microwave assisted synthesis and antifungal activity of some novel thioethers containing 1,2,4-triazolo [4,3-a]pyridine moiety. Lett. Drug Des. Discov., 2016, 13, 521-525.
[19]
Liu, X.H.; Pan, L.; Weng, J.Q.; Tan, C.X.; Li, Y.H.; Wang, B.L.; Li, Z.M. Synthesis, structure, and biological activity of novel (oxdi/tri)azoles derivatives containing 1,2,3-thiadiazole or methyl moiety. Mol. Divers., 2012, 16, 251-260.
[20]
Weng, J.Q.; Wang, L.; Liu, X.H. Synthesis, crystal structure and herbicidal activity of a 1, 2, 4-triazol-5(4h)-one derivative. J. Chem. Soc. Pak., 2012, 34, 1248-1252.
[21]
Liu, X.H.; Pan, L.; Tan, C.X.; Weng, J.Q.; Wang, B.L.; Li, Z.M. Synthesis, crystal structure, bioactivity and DFT calculation of new oxime ester derivatives containing cyclopropane moiety. Pestic. Biochem. Physiol., 2011, 101, 143-147.
[22]
Liu, X.H.; Pan, L.; Ma, Y.; Weng, J.Q.; Tan, C.X.; Li, Y.H.; Shi, Y.X.; Li, B.J.; Li, Z.M.; Zhang, Y.G. Design, synthesis, biological activities, and 3D-QSAR of new N,N '-diacylhydrazines containing 2-(2,4-dichlorophenoxy)propane moiety. Chem. Biol. Drug Des., 2011, 78, 689-694.
[23]
Tan, C.X.; Shi, Y.X.; Weng, J.Q.; Liu, X.H.; Li, B.J.; Zhao, W.G. Synthesis and antifungal activity of 1,2,4-triazole derivatives containing cyclopropane moiety. Lett. Drug Des. Discov., 2012, 9, 431-435.
[24]
Shen, Z.H.; Sun, Z.H.; Becnel, J.J.; Estep, A.; Wedge, D.E.; Tan, C.X.; Weng, J.Q.; Han, L.; Liu, X.H. Synthesis and mosquiticidal activity of novel hydrazone containing pyrimidine derivatives against Aedes aegypti. Lett. Drug Des. Discov., 2018, 15, 951-956.
[25]
Fang, Y.M.; Zhang, R.R.; Shen, Z.H.; Tan, C.X.; Weng, J.Q.; Xu, T.M.; Liu, X.H.; Huang, H.Y.; Wu, H.K. Synthesis and antifungal activity of some 6-tert-butyl-8-chloro-2, 3-dimethylquinolin-4-ol derivatives against Pyricularia oryae. Lett. Drug Des. Discov., 2018, 15, 1314-1318.
[26]
Liu, X-H.; Wang, Q.; Sun, Z.H.; Wedge, D.E.; Becnel, J.J.; Estep, A.S.; Tan, C.X.; Weng, J.Q. Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against Aedes aegypti. Pest Manag. Sci., 2017, 73, 953-959.
[27]
Fang, Y.M.; Zhang, R.R.; Shen, Z.H.; Wu, H.K.; Tan, C.X.; Weng, J.Q.; Xu, T.M.; Liu, X.H. Synthesis, antifungal activity, and sar study of some new 6-perfluoropropanyl quinoline derivatives. J. Heterocycl. Chem., 2018, 55, 240-245.
[28]
Zhai, Z.W.; Shi, Y.X.; Yang, M.Y.; Sun, Z.H.; Weng, J.Q.; Tan, C.X.; Liu, X.H.; Li, B.J.; Zhang, Y.G. Synthesis, crystal structure, dft studies and antifungal activity of 5- (4-cyclopropyl-5-((3-fluorobenzyl) sulfonyl)-4h-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole. Chin. J. Struct. Chem., 2016, 35, 25-33.
[29]
Shen, Z.H.; Shi, Y.X.; Yang, M.Y.; Sun, Z.H.; Weng, J.Q.; Tan, C.X.; Liu, X.H.; Li, B.J.; Zhao, W.G. Synthesis, crystal structure, dft studies and biological activity of a novel schiff base containing triazolo [4,3-a]pyridine Moiety. Chin. J. Struct. Chem., 2016, 35, 457-464.
[30]
Liu, X.H.; Tan, C.X.; Weng, J.Q. Synthesis, dimeric crystal structure, and fungicidal activity f-1-(4-methylphenyl)-2-(5-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio) ethanone. Phosphorus Sulfur Silicon Relat. Elem., 2011, 186, 558-564.
[31]
Liu, X.H.; Zhao, W.; Shen, Z.H.; Xing, J.H.; Yuan, J.; Yang, G.; Xu, T.M.; Peng, W.L. Synthesis, nematocidal activity and docking study of novel chiral 1-(3-chloropyridin-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives. Bioorg. Med. Chem. Lett., 2016, 26, 3626-3628.
[32]
Zhao, W.; Xing, J.H.; Xu, T.M.; Peng, W.L.; Liu, X.H. Synthesis and in vivo nematocidal evaluation of novel n-substituted 3-(trifluoromethyl)-1h-pyrazole-4-carboxamide derivatives. Front. Chem. Sci. Eng., 2017, 11, 363-368.
[33]
Liu, X.H.; Zhao, W.; Shen, Z.H.; Xing, J.H.; Xu, T.M.; Peng, W.L. Synthesis, nematocidal activity and SAR study of novel difluoromethylpyrazole carboxamide derivatives containing flexible alkyl chain moieties. Eur. J. Med. Chem., 2017, 125, 881-889.
[34]
Zhao, W.; Shen, Z.H.; Xu, T.M.; Peng, W.L.; Liu, X.H. Synthesis and nematocidal activity of novel pyrazole carboxamide derivatives against Meloidogyne incognita. Lett. Drug Des. Discov., 2017, 14, 323-329.
[35]
Zhao, W.; Shen, Z.H.; Xing, J.H.; Xu, T.M.; Peng, W.L.; Liu, X.H. Synthesis, characterization, nematocidal activity and docking study of novel pyrazole-4-carboxamide derivatives. Chin. J. Struct. Chem., 2017, 36, 423-428.
[36]
Zhao, W.; Shen, Z.H.; Xing, J.H.; Yang, G.; Xu, T.M.; Peng, W.L.; Liu, X.H. Synthesis and nematocidal activity of novel 1-(3-chloropyridin-2-yl)-3-(trifluoromethyl)-1H- pyrazole-4-carboxamide derivatives. Chem. Pap., 2017, 71, 921-928.
[37]
Cheng, L.; Zhao, W.; Shen, Z.H.; Xu, T.M.; Wu, H.K.; Peng, W.L.; Liu, X.H. Synthesis, nematocidal activity and docking study of novel pyrazole-4-carboxamide derivatives against meloidogyne incognita. Lett. Drug Des. Discov., 2019, 16, 29-35.
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