Novel 4-pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity

In recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure-activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity.

Twenty-seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L^-1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC₅₀ values of 2.04 to 15.2 μg mL^-1 . In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method.

It is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry.