title: Insecticidal and neuroblocking potencies of variants of the imidazolidine moiety of imidacloprid-related neonicotinoids and the relationship to partition coefficient and charge density on the pharmacophore.
abstract: The pharmacophore of the neonicotinoid insecticide imidacloprid, nitroiminoimidazolidine, was modified to heterocycles such as thiazolidine, pyrrolidine, dihydroimidazole, dihydrothiazole, and pyridone conjugated to nitroimine (=NNO2) or nitromethylene (=CHNO2). Their 6-chloro-3-pyridylmethyl or 5-chloro-3-thiazolylmethyl derivatives were examined for insecticidal activity against the American cockroach by injection and for neuroblocking activity using the cockroach ganglion. Most of the compounds having the neonicotinoidal pharmacophore exhibited insecticidal activity at the nanomolar level, which was enhanced in the presence of synergists, and high neuroblocking activity at the micromolar level. Quantitative analysis for the compounds showed that the neuroblocking potency is proportional both to the Mulliken charge on the nitro oxygen atom and to the partition coefficient log P value. The equation for the insecticidal versus neuroblocking potencies indicated that both potencies are related proportionally with each other when the other factors are the same.
authors.affiliation: Department of Chemistry, Faculty of Education, Gifu University, Gifu 501-1193, Japan. kagabus@gifu-u.ac.jp
authors.forename: Shinzo
authors.initials: S
authors.lastname: Kagabu
authors.forename: Rika
authors.initials: R
authors.lastname: Ishihara
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hieda
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nishimura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naruse
mesh_terms: D000691:Anabasine / Q000737:chemistry*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003058:Cockroaches; D007093:Imidazoles / Q000737:chemistry*; D048289:Imidazolidines / Q000737:chemistry* / Q000494:pharmacology; D007306:Insecticides; D000073943:Neonicotinoids; D009420:Nervous System / Q000187:drug effects*; D009574:Nitro Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D048289:Imidazolidines; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; C082359:imidacloprid; D000691:Anabasine