Novel Diphenyl Ether Carbonyl Ester Fragment as a Promising Skeleton Targeting Succinate Dehydrogenase.

Succinate dehydrogenase (SDH) is a globally recognized critical target for fungicides. Our research mainly focuses on discovering novel molecular skeletons targeting SDH. We designed a series of diphenyl ether ester derivatives that exhibit potential efficacy against by utilizing a bioisosteric approach. These results indicate that compounds with shorter linkers significantly enhance the antifungal activity. Furthermore, the antifungal potential of an ester-linked compound was superior to its amide and -(alkoxy) counterparts. Specifically, compound achieved a remarkable 92% efficacy in controlling at a dosage of 50 μg/mL with an EC value of 0.44 μg/mL, thus outperforming boscalid without negatively impacting rice growth. Moreover, caused significant damage to the mycelium and demonstrated an IC value of 1.69 μM against SDH, exhibiting efficacy comparable to that of boscalid. These results unveil a promising avenue for replacing traditional heterocyclic amide-based inhibitors, potentially heralding a new generation of SDH-targeting fungicides.