Design, synthesis and antifungal evaluation of novel pyrazole carboxamides with diarylamines scaffold as potent succinate dehydrogenase inhibitors

• Published in: Bioorganic & medicinal chemistry letters 2018-10, Vol.28 (18), p.3042-3045
• Main Authors: Zhang, Aigui, Zhou, Jingya, Tao, Ke, Hou, Taiping, Jin, Hong
• Format: Article
• Language: English
• Subjects: Amines - chemistry; Amines - pharmacology; Antifungal activities; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Dose-Response Relationship, Drug; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Fusarium - drug effects; Humans; Microbial Sensitivity Tests; Molecular Structure; Phytophthora infestans - drug effects; Pyrazole carboxamides; Pyrazoles - chemistry; Pyrazoles - pharmacology; Rhizoctonia - drug effects; Structure-Activity Relationship; Succinate Dehydrogenase - antagonists & inhibitors; Succinate Dehydrogenase - metabolism; Succinate dehydrogenase inhibitors; Synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.08.001

[Display omitted] •Sixteen novel substituted pyrazole carboxamides with diarylamines scaffold were designed and synthesized.•Compound 1c exhibited the highest antifungal activities against R. solani in vitro, superior to fluxapyroxad.•Compound 1c showed higher inhibition abilities against SDH than fluxapyroxad. Sixteen novel pyrazole carboxamides with diarylamines scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Fusarium oxysporum, Phytophthora infestans and Fusarium graminearum. Among them, compound 1c exhibited the highest antifungal activities against R. solani in vitro with EC50 value of 0.005 mg/L, superior to the commercially available fungicide fluxapyroxad (EC50 = 0.033 mg/L). And compound 1c (IC50 = 0.034 mg/L) showed higher inhibition abilities against succinate dehydrogenase than fluxapyroxad (IC50 = 0.037 mg/L). This study suggests that compound 1c could be regarded as a potential succinate dehydrogenase inhibitor.