Design of Scytalone Dehydratase-Inhibiting Rice Blast Fungicides

By targeting the enzyme scytalone dehydratase for inhibitor design, a series of highly efficacious rice blast fungicides were identified. Evaluation for disease control in a series of greenhouse and field assays led to the discovery of an exceptionally potent trifluoro-subtituted cyanoacetamide. Key to the design effort was the recognition that the lipophilicity of the chemistry was generally directly related to inhibitory potency but indirectly related to greenhouse efficacy. The incorporation of fluorine atoms during the design program afforded potent inhibitors and optimized physical-chemical properties important for bioavailability and superior control of rice blast disease.