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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 9: 2836 - 2844

DOI: https://doi.org/10.6023/cjoc202004013

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

  • Li Anbang ,
  • Li Zhongshan ,
  • Zhao Yang ,
  • Yao Tingting ,
  • Cheng Jingli ,
  • Zhao Jinhao
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  • Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310058

Received date: 2020-04-09

  Revised date: 2020-05-16

  Online published: 2020-06-28

Supported by

Project 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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Abstract

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.

Key words： succinate dehydrogenase inhibitor; pyrazole-furan carboxamide; antifungal activity; molecular docking

Cite this article

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

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