Location: Natural Products Utilization ResearchTitle: Novel 4-pyrazole carboxamide derivatives containing flexible chain motif: Design, synthesis, and antifungal activity
|LIU, XING-HAI - Zhejiang University|
|QIAO, LI - Zhejiang University|
|ZHAI, ZHI-WEN - Zhejiang University|
|CAI, PENG-PENG - Zhejiang University|
|TAN, CHEN-XIA - Zhejiang University|
|WENG, JIAN-QUAN - Zhejiang University|
|HAN, LIANG - Zhejiang University|
|WU, HONG-KE - Zhejiang University|
Submitted to: Pest Management Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2019
Publication Date: 5/3/2019
Citation: Liu, X., Qiao, L., Zhai, Z., Cai, P., Cantrell, C.L., Tan, C., Weng, J., Han, L., Wu, H. 2019. Novel 4-pyrazole carboxamide derivatives containing flexible chain motif: Design, synthesis, and antifungal activity. Pest Management Science. https://doi.org/10.1002/ps.5463.
Interpretive Summary: Due to the long term use of fungicides in agriculture, fungicide-resistance has increased in recent years. It is urgent to develop novel highly active compounds with high effectiveness, low toxicity and which are environmentally friendly in order to overcome the resistance problems. Since the first fungicide carboxin, which targets succinate dehydrogenase (SDH) was discovered in the 1960s, many SDHI fungicides had been developed to protect fruit, vegetable and other crops. Many of the recent SDHI fungicides contain a pyrazole ring and a carboxamide. In this paper, the carboxamide group was modified in order to find novel structure pyrazole carboxamide derivatives. Twenty seven novel pyrazole carboxamide derivatives were designed and synthesized. Some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum and other fungal pathogens.
Technical Abstract: BACKGROUND: In recent years, pyrazole carboxamide derivatives have possessed excellent fungicidal activity which targets succinate dehydrogenase (SDH). In the process of designing new fungicides, the carboxamide group was modified in order to find novel structure pyrazole carboxamide derivatives. RESULTS: Twenty seven novel pyrazole carboxamide derivatives were designed and synthesized. Fungicidal activities of these compounds were tested against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Sclerotinia sclerotiorum, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola and Physalospora piricola, particular compounds exhibited significant inhibitory activity at 50 mg/L. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 µg mL-1. High activities were also found against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Furthermore, enzyme docking modeling studies were established to study the structure-activity relationship of the title compounds. CONCLUSION: It is possible that pyrazole carboxamide derivatives, which possess good activity against Sclerotinia sclerotiorum, may become novel lead compounds for the development of fungicides with further structure modification.