Design, Synthesis, and Fungicidal Evaluation of Novel Pyrazole-furan and Pyrazole-pyrrole Carboxamide as Succinate Dehydrogenase Inhibitors

• Published in: Journal of agricultural and food chemistry Vol. 65; no. 26; pp. 5397 - 5403
• Main Authors: Yao, Ting-Ting, Xiao, Dou-Xin, Li, Zhong-Shan, Cheng, Jing-Li, Fang, Shao-Wei, Du, Yong-Jun, Zhao, Jin-Hao, Dong, Xiao-Wu, Zhu, Guo-Nian
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 05.07.2017; Amer Chemical Soc
• Subjects: Agriculture; Agriculture, Multidisciplinary; Chemistry; Chemistry, Applied; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Food Science & Technology; Fungi - drug effects; Fungicides, Industrial - chemical synthesis; Fungicides, Industrial - chemistry; Fungicides, Industrial - pharmacology; Furans - chemistry; Life Sciences & Biomedicine; Molecular Structure; Physical Sciences; Pyrazoles - chemistry; Science & Technology; Structure-Activity Relationship; Succinate Dehydrogenase - antagonists & inhibitors; Succinate Dehydrogenase - chemistry; synthesis; succinate dehydrogenase inhibitors; molecular docking; scaffold hopping; fungicidal activity; BOTRYTIS-CINEREA; ANTIFUNGAL ACTIVITY; BASE-LINE SENSITIVITY; INSECTICIDAL ACTIVITY; POTENT; STRUCTURE-BASED DISCOVERY; BIOLOGICAL-ACTIVITY; RESISTANCE; DERIVATIVES; UBIQUINONE OXIDOREDUCTASE INHIBITORS
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.7b01251

The identification of novel succinate dehydrogenase (SDH) inhibitors represents one of the most attractive directions in the field of fungicide research and development. During our continuous efforts to pursue inhibitors belonging to this class, some structurally novel pyrazole-furan carboxamide and pyrazole-pyrrole carboxamide derivatives have been discovered via the introduction of scaffold hopping and bioisosterism to compound 1, a remarkably potent lead obtained by pharmacophore-based virtual screening. As a result of the evaluation against three destructive fungi, including Sclerotinia sclerotiorum, Rhizoctonia solani, and Pyricularia grisea, a majority of them displayed potent fungicidal activities. In particular, compounds 12I-i, 12III-f, and 12III-o exhibited excellent fungicidal activity against S. sclerotiorum and R. solani comparable to that of commercial SDHI thifluzamide and 1.