title: Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor.
abstract: A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan. nishiwaki.hisashi.mg@ehime-u.ac.jp
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nishiwaki
authors.forename: Mituhiro
authors.initials: M
authors.lastname: Kuriyama
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nagaoka
authors.forename: Akira
authors.initials: A
authors.lastname: Kato
authors.forename: Miki
authors.initials: M
authors.lastname: Akamatsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamauchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shuto
mesh_terms: D000478:Alkylation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006793:Houseflies / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D048289:Imidazolidines / Q000737:chemistry*; D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D007093:Imidazoles; D048289:Imidazolidines; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D011978:Receptors, Nicotinic; C082359:imidacloprid