Scaffold-Hopping Approach To Identify New Chemotypes of Dimpropyridaz

Dimpropyridaz is a pyrazole carboxamide insecticide with a novel mode of action, currently under worldwide development by BASF, providing excellent activity against sucking pests. A series of dimpropyridaz analogues were designed to investigate the impact of bioisosteric heterocyclic replacements on the biological activity and molecular properties. Focus was given to prepare analogues where the 4-pyridazinyl moiety was replaced by 5-pyrimidinyl, 2-pyrimidinyl, 3-pyridazinyl, and 2-pyrazinyl groups. Five different synthetic routes were developed for the preparation of these analogues, delivering the target compounds in moderate to good yields. We explained some aspects of the observed structure-activity relationship by a density functional theory (DFT) calculation and DFT-derived Multiwfn and VMD program models. These findings provide first insights into the important role of the 4-pyridazinyl heterocyclic moiety in the pyrazole carboxamide insecticide chemical class and the mechanism of action of dimpropyridaz.