The discovery of metyltetraprole: Reconstruction of the quinone outside inhibitor extended pharmacophore to overcome QoI-resistant strains

Abstract Metyltetraprole is Sumitomo’s new quinone outside inhibitor (QoI) fungicide designed to overcome existing QoI-resistant strains. The compound, an extended pharmacophore, is characterized by a unique 3-substituted central ring with a tetrazolinone moiety. This pharmacophore is reconstructed to retain the potent activity against the QoI-resistant G143A haplotype of cytochrome b. The resistance factor [(EC50 of G143A)/(EC50 of sensitive strain)] of metyltetraprole is 100. Metyltetraprole is being developed globally as Pavecto with the first registration and sales anticipated in 2021. The discovery project concept, optimization of chemical structures, and the biological profile will be reviewed.