Discovery of HNPC-A9229: A Novel Pyridin-2-yloxy-Based Pyrimidin-4-amine Fungicide.

To search for novel pesticides, the synthesis around commercialized insecticide tebufenpyrad accidentally led us to the discovery of the fungicidal lead compound, 3-ethyl-1-methyl--((2-phenylthiazol-4-yl)methyl)-1-pyrazole-5-carboxamide () and its pyrimidin-4-amine-based optimization derivative 5-chloro-2,6-dimethyl--(1-(2-(p-tolyl)thiazol-4-yl)ethyl)pyrimidin-4-amine (). Compound not only demonstrates fungicidal activity superior to commercial fungicides such as diflumetorim but also exhibits the good features that come with pyrimidin-4-amines, such as unique modes of action and no cross-resistance to other pesticide classes. However, is highly toxic to rats. Further optimization of by introducing pyridin-2-yloxy substructure finally led to the discovery of - (-) (5-chloro--(1-((3-chloropyridin-2-yl)oxy)propan-2-yl)-6-(difluoromethyl)pyrimidin-4-amine). - exhibits excellent fungicidal activities with EC values of 0.16 mg/L against and 1.14 mg/L against , respectively. Not only that its fungicidal potency is significantly superior to or comparable to commercial fungicides including diflumetorim, tebuconazole, flusilazole, and isopyrazam, - possesses low toxicity to rats.