Discovery of pyridachlometyl: A new class of pyridazine fungicides

[Display omitted] •Bioisosterical transformation was attempted during fungicide discovery research.•[1,2,4]triazolo[1,5-a]pyrimidine was transformed into pyridazine.•Structural simplification led us to a cost-effective compound, pyridachlometyl.•Pyridachlometyl is expected to be commercially available in 2024. Pyridachlometyl is a unique pyridazine fungicide with a novel mode of action. Herein, we describe the pathway for the invention of pyridachlometyl. First, we identified a diphenyl-imidazo[1,2-a]pyrimidine as our proprietary lead with potent fungicidal activity. Then, aiming to simplify the chemical structure, we applied judicious estimations to explore monocyclic heterocycles as pharmacophores. This enabled the identification of a novel class of tetrasubstituted pyridazine compounds with potent fungicidal activity, likely retaining the same mode of action as the aforementioned compounds. The findings indicated bioisosteric similarity between diphenyl-imidazo[1,2-a]pyrimidine and pyridazine. Further structure–activity and mammalian safety investigations of pyridazine compounds resulted in the discovery of pyridachlometyl as a candidate for commercial development.