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

Lizeng Wang; Shixiang Pan; Zhaokai Yang; Aiying Guan; Xufeng Sun; Jinbo Zhang; Zhinian Li; Changling Liu; Xinling Yang

doi:10.2174/1570179420666230327145745

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

Curr Org Synth. 2023 Mar 27. doi: 10.2174/1570179420666230327145745. Online ahead of print.

Authors

Lizeng Wang^{1

2}, Shixiang Pan¹, Zhaokai Yang¹, Aiying Guan², Xufeng Sun², Jinbo Zhang², Zhinian Li², Changling Liu², Xinling Yang¹

Affiliations

¹ Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
² State Key Laboratory of the Discovery and Development of Novel Pesticide, Shenyang Sinochem Agrochemicals R&D Co. Ltd., Shenyang 110021, China.

PMID: 36974411
DOI: 10.2174/1570179420666230327145745

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.