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Current Organic Synthesis

Author(s): Lizeng Wang, Shixiang Pan, Zhaokai Yang, Aiying Guan, Xufeng Sun, Jinbo Zhang, Zhinian Li, Changling Liu* and Xinling Yang*

DOI: 10.2174/1570179420666230327145745

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A Potential Fungicide against Pseudoperonospora cubensis: Design, Synthesis and 3D-QSAR of New Pyrazole-5-carboxamide Derivatives

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Abstract

Background: Downy mildew is one of the major fungi causing significant economic losses to crops. The resistance of this fungus to current fungicides is increasing and new fungicides with a unique mode of action are needed.

Objective: To find a novel pyrazole amide derivative as a potential fungicide.

Methods: A series of pyrazole-5-carboxamide derivatives containing a diaryl ether were designed and synthesized by the Intermediate derivatization method (IDM). Their fungicidal activities against Pseudoperonospora cubensis (P. cubensis, cucumber downy mildew) were evaluated in the greenhouse.

Results: Bioassays indicated that several compounds exhibited excellent fungicidal activity against P. cubensis in vivo. In particular, T24 (EC50 = 0.88 mg·L-1) had the highest activity compared with Dimethomorph and Fluazinam and other analogues. The relationship between the activity and the structure of these derivatives was analyzed, and an accurate and reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) model was established to determine that electrostatic and steric fields had important effects on the improvement of fungicidal activity.

Conclusion: The novel pyrazole-5-carboxamide derivative T24 can be considered a potential fungicide for P. cubensis control.

Keywords: pyrazole-5-carboxamide, diaryl ether, synthesis, fungicidal activity, Pseudoperonospora Cubensis, 3D-QSAR.

Graphical Abstract

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