Potency and selectivity of trifluoroacetylimino and pyrazinoylimino nicotinic insecticides and their fit at a unique binding site niche.

Neonicotinoid agonists with a nitroimino or cyanoimino pharmacophore are the newest of the four most important classes of insecticides. Our studies on the nicotinic receptor structure in the neonicotinoid-bound state revealed a unique niche of about 6 A depth beyond the nitro oxygen or cyano nitrogen tip. The N-substituted imino pharmacophore was therefore extended to fill the gap. Excellent target site selectivity with high insecticidal activity and low toxicity to mammals were achieved rivaling those of the current neonicotinoid insecticides as illustrated here by 3-(6-chloropyridin-3-ylmethyl)-2-trifluoroacetyliminothiazoline and its pyrazinoylimino analogue.