Design, synthesis, and antifungal activity of novel cinnamon–pyrazole carboxamide derivatives

• DOI: 10.1002/ddr.21469
• Publication Date: 2018-09-26T13:46:52Z
• Authors: Zi‐Li Ren; Hao Liu; Di Jiao; Hao‐Tian Hu; Wei Wang; Jie‐Xiu Gong; Ai‐Li Wang; Hai‐Qun Cao; Xian‐Hai Lv
• Keywords: Molecular Docking Simulation; 0303 health sciences; 03 medical and health sciences; Antifungal Agents; Cinnamates; Drug Design; Colletotrichum; Quantitative Structure-Activity Relationship; Carboxin; Plant Diseases; Rhizoctonia

AbstractHit, Lead & Candidate DiscoveryTo discover succinate dehydrogenase inhibitors with a novel structure, we introduced cinnamic acid structure to optimize the lead structure1and synthesized four series of cinnamon–pyrazole carboxamide derivatives. The bioassay data showed that compounds (E)‐N‐(1‐[4‐chlorophenyl]‐4‐cyano‐1H‐pyrazol‐5‐yl)‐3‐(2‐fluorophenyl) acrylamide (5III‐d)and (E)‐3‐(2‐chlorophenyl)‐N‐(1‐[4‐chlorophenyl]‐4‐cyano‐1H‐pyrazol‐5‐yl) acrylamide (5III‐f)showed the significant antifungal activity against three fungi. In addition,5III‐dand5III‐fexhibited the excellent inhibitory effect against succinate dehydrogenase (SDH) enzymes with IC50values ranging from 19.4 to 28.7 μM. The study demonstrates that the chlorine substituent group is present on both the phenyl and pyrazole rings that have a very good effect on the antifungal effect, and the compounds5III‐dand5III‐fcan act as potential SDH inhibitors (SDHI) and throw a sprat for a new generation of SDHI.