The production of many agricultural crops requires the use of commercial fungicides to control fungal diseases that can drastically reduce crop quality and yield. There is a need for new commercial fungicides with novel modes of action because the various fungi that cause such diseases eventually develop resistance to commercial fungicides. In a recent research effort, we discovered that compound 1 exhibited potent control of SEPTTR in wheat. A SEPTTR mutagenesis study with compound 1 produced seven different mutants that exhibited significant resistance to compound 1. Remarkably, all seven of these SEPTTR mutants exhibited mutations in SEPTTR aurora kinase. In a focused SAR study of structure 1, we discovered other compounds 2 that exhibited various levels of SEPTTR control in wheat. We demonstrated that the SEPTTR control provided by compounds 2 was correlated to their ability to inhibit SEPTTR aurora kinase. Unfortunately, we found that the best SEPTTR fungicides in this chemical space were also potent inhibitors of human aurora kinase and many other human kinases.

Fungicidal kinase inhibitors

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