Citation: Li Anbang, Li Zhongshan, Zhao Yang, Yao Tingting, Cheng Jingli, Zhao Jinhao. Design, Synthesis and Antifungal Activity of Novel Pyrazole-Thiophene Carboxamide Derivatives[J]. Chinese Journal of Organic Chemistry, ;2020, 40(9): 2836-2844. doi: 10.6023/cjoc202004013 shu

Design, Synthesis and Antifungal Activity of Novel Pyrazole-Thiophene Carboxamide Derivatives

Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310058

Corresponding author: Cheng Jingli, chengjingli@zju.edu.cn Zhao Jinhao, jinhaozhao@zju.edu.cn
Received Date: 9 April 2020
Revised Date: 16 May 2020
Available Online: 24 June 2020
Fund Project: the Natural Science Foundation of Zhejiang Province LY19C140006the National Natural Science Foundation of China 31872022the National Key Research & Development Program of China 2017YFD0200505Project supported by the Natural Science Foundation of Zhejiang Province (No. LY19C140006), the National Key Research & Development Program of China (No. 2017YFD0200505) and the National Natural Science Foundation of China (No. 31872022)

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Succinate dehydrogenase inhibitor is a low-toxic and high active fungicide. In order to develop novel and broad-spectrum succinate dehydrogenase inhibitor (SDHI) fungicides, thiophene was introduced into the structure of pyrazole carboxamide fungicides. Twenty four pyrazole-thiophene carboxamides were designed, synthesized and characterized by ¹H NMR, ¹³C NMR and HRMS. The crystal structure of N-(4-methoxyphenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7i) was determined by X-ray diffraction. The antifungal activity of all the synthesized compounds was determined against six plant pathogenic fungi, and preliminary bioassays suggested that some compounds exhibited good antifungal activity against Rhizoctonia solani, Fusarium graminearum and Botrytis cinerea. Among them, N-(4-fluorophenethyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7c) exhibited the best antifungal activities against R. solani in vitro with EC₅₀ value of 11.6 μmol/L, and N-(2-fluorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7j) against F. graminearum with EC₅₀ value of 28.9 μmol/L. And N-(4-chlorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7h) showed similar inhibition abilities with thifluzamide against B. cinerea with EC₅₀ value of 21.3 μmol/L. The molecular docking results showed that the high antifungal activitie compounds form stronger interactions with important amino acid residues of succinate dehydrogenase.
- succinate dehydrogenase inhibitor,
- pyrazole-furan carboxamide,
- antifungal activity,
- molecular docking
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