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. 2015 May 8;20(5):8395-408.
doi: 10.3390/molecules20058395.

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

Shijie Du  1 , Zaimin Tian  2 , Dongyan Yang  3 , Xiuyun Li  4 , Hong Li  5 , Changqing Jia  6 , Chuanliang Che  7 , Mian Wang  8 , Zhaohai Qin  9
Affiliations

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

Shijie Du et al. Molecules. .

Abstract

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

Keywords: CoMFA; SDHIs; fungicidal activity; molecular docking.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Commercial available 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amide fungicides.
Scheme 1
Scheme 1
Synthetic procedure for target compounds 3a.
Scheme 2
Scheme 2
Synthetic procedure for target compounds 5a–5g.
Scheme 3
Scheme 3
Synthetic procedure for target compounds 9a–9n.
Scheme 4
Scheme 4
Synthetic procedure for carboxylic acid chloride 10.
Figure 2
Figure 2
Topomer CoMFA contour maps around the amine moiety. (a) steric field around the amine moiety of 9m; (b) electrostatic field around the amine moiety of 9m.
Figure 3
Figure 3
Surflex-Docking of compound 9m to complex II. (a) Interaction of 9m and amino acid residues near the ligands (3D diagram); (b) Connolly surface of complex II with compound 9m and boscalid shown as a stick model.
See this image and copyright information in PMC

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