N-Hetaryl-[2(1H)-pyridinyliden]cyanamides: A New Class of Systemic Insecticides.

The new chemical class N-hetaryl-[2(1H)-pyridinylidene]cyanamides were inspired by the long known five-ring structure 2-chloro-5-[2-(nitro-methylene)-1-imidazolidinyl]-pyridine (Shell) and the current development candidate flupyrimin (Meiji Seika Pharma) via scaffold hopping and the concept for designing "shortened structures" by omitting the "methylene link" as a structural feature. The most active N-hetaryl-[2(1H)-pyridinylidene]cyanamides can be synthesized on a technical scale by a simple manufacturing procedure. As full nicotinic acetylcholine receptor (nAChR) agonists, the compounds bind with low affinity at the orthosteric binding site of nAChR. In molecular modeling studies, structural differences are visible in the superposition of active N-[6'-(trifluoromethyl)[1(2H),3'-bipyridin]-2-ylidene]cyanamide onto imidacloprid (IMD) and sulfoxaflor (SXF) in bound conformation. On the basis of 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 modeling investigations (Fukui functions, dipole moments, and electrostatic potentials), there is a broad scope for structure optimization of the chemical class leading to proposals for novel bicyclic insecticides.

Insecticidal heterolignans--tubuline polymerization inhibitors with activity against chewing pests.

Starting from natural product podophyllotoxin 1 substituted heterolignans were identified with promising insecticidal in vivo activity. The impact of substitution in each segment of the core structure was investigated in a detailed SAR study, and variation of substituents in both aromatic moieties afforded derivatives 5 and 43 with broad insecticidal activity against lepidopteran and coleopteran species. In vitro measurements supported by modeling studies indicate that heterolignans 3-134 act as tubuline polymerization inhibitors interacting with the colchicine-binding site. Insect specific structure-activity effects were observed showing that the insecticidal SAR described herein differs from reported cytotoxicity studies.

Factors affecting the field performance of an attracticide against the codling moth Cydia pomonella.

Factors affecting the efficacy of an attracticide strategy for the control of the codling moth Cydia pomonella L (Lepidoptera: Tortricidae) were investigated using laboratory and field experiments. The sex-pheromone-based insect-control strategy utilises 100-microliters droplets of a sticky, paste-like formulation containing 1 mg g-1 (E,E)-8,10-dodecadien-1-ol (codlemone) as an attractant for male moths and 40 mg g-1 cyfluthrin, a contact insecticide, applied to branches in the upper parts of the tree crown. The longevity of the treatment under field conditions was assessed in the laboratory by biological testing of variously aged samples of the attracticide formulation which had been applied to the bark of apple trees growing in commercial orchards. Electroantennogram responses of male moth antennae were used to compare codlemone release from the attracticide after different lengths of environmental exposure. Changes in insecticidal efficacy of the same samples were assessed with reference to the speed of knockdown (KT50) and the mortalities after 48 h among populations of male moths confined in cages containing samples of fresh and field-aged formulations. Gradual declines in both the amount of pheromone released and insecticidal activity were observed over the 10-week period of the experiments. Various factors associated with the behaviour of codling moths in the field which might influence the attracticide strategy were also investigated. Although the vertical position of attracticide sources within apple trees had a strong influence on their attractiveness, their horizontal position had none. Results of field trials showed that efficacy of the attracticide depends on the population density of the pest. Under the conditions of the current study a density of three or more sources per tree (= 4500 sources per ha) was required to attain satisfactory levels of codling moth control.

Syntheses of depsipeptide analogues of the insect neuropeptide proctolin.

Four depsipeptide analogues of the insect neuropeptide proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) have been prepared, containing a single ester linkage between Arg(1) and Tyr(2), Tyr(2) and Leu(3), and between Pro(4) and Thr(5), respectively. A didepsipentapeptide containing an ester linkage between Tyr(2) and Leu(3) and between Pro(4) and Thr(5), has also been prepared. The depsipeptide 4 is the first example of a backbone-modified proctolin analogue which shows full myotropic activity.