The damage caused by plant-parasitic nematodes leads to severe agricultural yield losses worldwide. To tackle the threat of nematodes, a discovery program was started at Syngenta which led to the development of TYMIRIUM® technology, a new nematicide and fungicide that obtained first registrations in 2022.

The active ingredient is Cyclobutrifluram, a chiral phenyl-cyclobutyl-pyridineamide, which displays broad spectrum efficacy against the plant parasitic nematodes and soil-borne diseases – particularly the Fusarium species.

We describe the discovery of this molecule from hit identification through lead exploration and lead optimization phases.

This includes the establishment of the nematicide screening platform together with the generation of a focused nematicide screening library, and the rapid identification of the mode of action for the lead series. Target identification using biochemical and genetic methods, allowed the development of an in vitro assay for SAR analysis and the development of homology models for structure-based design. This established a design and analysis toolbox for accurate molecular design coupled to synthesis. Our collaborative, multi-disciplinary approach led to the discovery of TYMIRIUM® technology.