title: Novel phthalamides containing sulfiliminyl moieties and derivatives as potential ryanodine receptor modulators.
abstract: To tackle the serious challenge of insect resistance and stricter environmental regulations, innovating a new eco-friendly insecticide is urgently required. A series of new phthalamides containing sulfiliminyl and sulfoximinyl moieties were designed and synthesized. In total, 30 new structures were characterized by 1H NMR spectra and HRMS. The bioassay results indicated that some title compounds exhibited excellent insecticidal activities against oriental armyworm (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)). 4a showed the same larvicidal level as that of commercial flubendiamide as a control. 7a and 9a exhibited outstanding activity against diamondback moth. The LC50 values of 7a and 9a were 8.33 × 10(−8) and 2.34 × 10(−8) mg L(−1), respectively, lower than that of flubendiamide (1.25 × 10(−7) mg L(−1)). The effects of 4a, 7a and 9a on intracellular calcium of neurons from the beet armyworm (Spodoptera exigua) indicated that these title compounds activate the receptor-operated calcium channel. The calcium ions efflux from the calcium store on endoplasmic reticulum (ER) when treated with novel compounds. The results of CoMFA calculation showed that N-cyanosulfilimines and N-trifluoroacetylsulfoximines might be of importance to the larvicidal activity. The present work demonstrated that structures containing sulfiliminyl and sulfoximinyl moieties can be considered as lead compounds for the development of new insect ryanodine receptor modulators.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China. nkzml@vip.163.com.
authors.forename: Sha
authors.initials: S
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Yan
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Zhehui
authors.initials: Z
authors.lastname: Jia
authors.forename: Baolei
authors.initials: B
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Lixia
authors.initials: L
authors.lastname: Xiong
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Li
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Li
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015195:Drug Design; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D019476:Insect Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007306:Insecticides / Q000138:chemical synthesis / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010795:Phthalic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000494:pharmacology; D005466:Fluorocarbons; D010797:Phthalimides
chemical_list: D000577:Amides; D001549:Benzamides; D002118:Calcium; D019476:Insect Proteins; D007306:Insecticides; D010795:Phthalic Acids; D019837:Ryanodine Receptor Calcium Release Channel; D013450:Sulfones; C508762:flubendiamide; D005466:Fluorocarbons; D010797:Phthalimides