The discovery of Cyclobutrifluram, a new molecule with powerful activity against nematodes and diseases
Anthony J Flemming, Marcus Guest, Torsten Luksch, Anthony C. O’Sullivan, Claudio Screpanti, Raphaël Dumeunier, Matthias Gaberthüel, Edouard Godineau, Philippa H Harlow, André Jeanguenat, Benedikt Kurtz, Peter Maienfisch, Régis Mondière, Andy Pierce, Brigitte Slaats, Tomáš Šmejkal, Olivier Loiseleur
Abstract
Syngenta responded to significant agricultural losses caused by plant-parasitic nematodes by initiating a next-generation nematicide discovery program. This effort led to the development of TYMIRIUM® technology, a nematicide and fungicide solution containing Cyclobutrifluram as its active ingredient. In 2022, this innovative solution received its first registration. Cyclobutrifluram, a chiral phenyl-cyclobutyl-pyridineamide, demonstrates wide-ranging effectiveness against all economically important plant parasitic nematodes and several soil-borne diseases, particularly those caused by Fusarium species. The discovery of this molecule involved hit the identification, lead exploration, and optimization stages, which made use of various methods such as phenotypic nematicide screening platforms, targeted screening libraries, rapid target identification through biochemical and genetic approaches, in vitro assays for structure-activity relationship (SAR) analysis, and homology models for structure-based design. This multi-disciplinary approach led to the successful identification of Cyclobutrifluram as the key component in TYMIRIUM® technology. © 2025 Society of Chemical Industry.