一种潜在的抗瓜类霜霉病菌的杀菌剂：新型吡唑-5-甲酰胺衍生物的设计、合成及三维定量构效关系研究

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

作者信息

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

机构信息

Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.

State Key Laboratory of the Discovery and Development of Novel Pesticide, Shenyang Sinochem Agrochemicals R&D Co. Ltd., Shenyang 110021, China.

出版信息

Curr Org Synth. 2023 Mar 27. doi: 10.2174/1570179420666230327145745.

DOI:10.2174/1570179420666230327145745

PMID:36974411

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 (EC = 0.88 mg L) 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.

摘要

背景

霜霉病是导致农作物重大经济损失的主要真菌之一。这种真菌对当前杀菌剂的抗性正在增加，因此需要具有独特作用方式的新型杀菌剂。

目的

寻找一种新型吡唑酰胺衍生物作为潜在的杀菌剂。

方法

采用中间体衍生化法（IDM）设计并合成了一系列含二芳基醚的吡唑-5-甲酰胺衍生物。在温室中评估了它们对古巴假霜霉（黄瓜霜霉病病原菌）的杀菌活性。

结果

生物测定表明，几种化合物在体内对古巴假霜霉表现出优异的杀菌活性。特别是，与烯酰吗啉、氟啶胺和其他类似物相比，T24（EC = 0.88 mg/L）具有最高的活性。分析了这些衍生物的活性与结构之间的关系，并建立了准确可靠的三维定量构效关系（3D-QSAR）模型，以确定静电场和立体场对提高杀菌活性具有重要影响。