Novel 5-(Trifluoromethyl)-1,2,4-Oxadiazole Substituted Benzamide Derivatives Containing 5-(Trifluoromethyl)-1,2,4-Oxadiazole Moiety: Design, Synthesis, Anti-Rust and In Silico Study

Trifluoromethyloxadiazole compounds (TFMO) are a class of anti-rust disease targeting histone deacetylases inhibitors (HDACs). In this paper, a series of 5-(trifluoromethyl)-1,2,4-oxadiazole substituted benzamide derivatives containing 5-(trifluoromethyl)-1,2,4-oxadiazole moiety were designed and synthesized. Anti-rust bioassay results showed some of them possessed excellent activities against Puccinia sorghi at 200 mg/L. Furthermore, the structure–activity relationship was established using in silico methods, and the most active compound binding mode was carried out based on the crystal structure of human HDAC1, human HDAC4, and human HDAC6. This work provided an excellent fungicide against rust for further optimization.