FM ‐3224: A potent triazolinone‐based fungicide with broad‐spectrum activity and computational support for putative dual‐target binding

Abstract BACKGROUND Asian soybean rust (ASR), caused by Phakopsora pachyrhizi , remains difficult to control because resistance has reduced the effectiveness of several major fungicide classes. In this study, we designed 1,2,4‐oxadiazole derivatives bearing tetrazolinone or triazolinone fragments through fragment recombination and then explored the putative target‐binding characteristics of the lead compound by computational methods. RESULTS Twenty‐four target compounds were synthesized and evaluated against P. pachyrhizi , Pseudoperonospora cubensis , Blumeria graminis , and Corynespora cassiicola . Among them, the triazolinone derivative B9 (FM‐3224) showed the best overall performance. Against P. pachyrhizi , FM‐3224 gave an EC 50 of 0.82 mg L −1 , compared with 2.65 mg L −1 for flufenoxadiazam and 3.08 mg L −1 for metyltetraprole. FM‐3224 also showed strong activity against the other three pathogens. Docking analyses suggested favorable interactions of FM‐3224 with HDAC 4 and the Saccharomyces cerevisiae bc1 complex, and density functional theory (DFT) calculations indicated a relatively small HOMO–LUMO gap (0.16815 a.u.), suggesting comparatively favorable electronic responsiveness. CONCLUSION FM‐3224 is a promising broad‐spectrum lead compound. The biological results establish its strong fungicidal potential, whereas the docking and DFT analyses provide computational support for further investigation of its putative dual‐target binding mode. © 2026 Society of Chemical Industry.