There was a “dogma” saying “... strong insecticidal activity requires on a methylene link in relevant nicotinic acetylcholine receptor (nAChR) agonists”. Therefore, the significant effectiveness of the new chemical class N-hetaryl-2(1H)-pyridinylidene]-cyanamides was unexpected. Its chemistry was inspired by the old 5-ring structure 2-chloro-5-[2-(nitro-methylene)-1-imidazolidinyl]-pyridine (Shell, 1994) and the current development candidate flupyrimin (Meiji Seika Pharma) via scaffold hopping and the concept for designing “shortened structures” by omit the “methylene link” as structural feature. The most active N-hetaryl-2(1H)-pyridinylidene]-cyanamides can be synthesized on a technical scale by a simple procedure. As full nAChR agonists the members of the new chemical class bind with low affinity at the ortho-steric binding site of the nAChR. However, in molecular modeling studies structural differences are visible in superposition of the active N-[6′-(trifluoromethyl)[1(2H),3′-bipyridin]-2-ylidene]-cyanamide onto imidacloprid and sulfoxaflor in bound conformation. Based on their physicochemical properties, the most active xylem-systemic candidates offer excellent aphicidal activity in vegetables and cotton, when applied as a foliar spray, by soil drench application or in particular as seed dressing for seed treatment uses. Selected candidates show good plant compatibility and reveal a better risk profile with respect to bee pollinators than the majority of currently registered nAChR competitive modulators for seed treatment uses. Applied as a seed dressing in greenhouse profiling, good to excellent control of different aphid species has been observed. In field trials, an interesting level of activity potential against cereal grain aphids (inclusive virus vector control), corn rootworm and wireworm could be demonstrated. According to molecular modelling investigations (Fukui functions, dipole moments, electrostatic potentials), there is a broad scope for structure optimization of the chemical class leading to proposals for novel bicyclic insecticides.

Prof. Dr. Peter Jeschke

BAYER AG, Crop Science

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