Novel Anthranilic Diamide Scaffolds Containing N-Substituted Phenylpyrazole as Potential Ryanodine Receptor Activators.

To discover potent insecticides targeting ryanodine receptors (RyRs), a series of novel anthranilic diamides analogues (12a-12u) containing N-substituted phenylpyrazole were designed and synthesized. These compounds were characterized by (1)H NMR, (13)C NMR, and HRMS, and the structure of compound 12u was confirmed by X-ray diffraction. Their insecticidal activities indicated that these compounds displayed moderate to excellent activities. In particular, 12i showed 100 and 37% larvicidal activities against oriental armyworm (Mythimna separata) at 0.25 and 0.05 mg L(-1), equivalent to that of chlorantraniliprole (100%, 0.25 mg L(-1); and 33%, 0.05 mg L(-1)). The activity of 12i against diamondback moth (Plutella xylostella) was 95% at 0.05 mg L(-1), whereas the control was 100% at 0.05 mg L(-1). The calcium-imaging technique experiment results showed that the effects of 12i on the intracellular calcium ion concentration ([Ca(2+)]i) in neurons were concentration-dependent. After the central neurons of Helicoverpa armigera were dyed by loading with fluo-5N and treated with 12i, the free calcium released in endoplasmic reticulum indicated the target of compound 12i is RyRs or IP3Rs. The activation of RyRs by natural ryanodine completely blocked the calcium release induced by 12i, which indicated that RyRs in the central neurons of H. armigera third-instar larvae is the possible target of compound 12i.

[1]  Zhi‐Wen Zhai,et al.  Facile and efficient synthesis and herbicidal activity determination of novel 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one derivatives via microwave irradiation. , 2015, Bioorganic & medicinal chemistry letters.

[2]  Kai Chen,et al.  Synthesis, insecticidal activities and structure-activity relationship studies of novel anthranilic diamides containing pyridylpyrazole-4-carboxamide. , 2015, Pest management science.

[3]  S. Oh,et al.  Design, synthesis, and biological evaluation of a series of alkoxy-3-indolylacetic acids as peroxisome proliferator-activated receptor γ/δ agonists. , 2015, Bioorganic & medicinal chemistry.

[4]  Jianquan Weng,et al.  Synthesis, crystal structure, herbicidal activities and 3D-QSAR study of some novel 1,2,4-triazolo[4,3-a]pyridine derivatives. , 2015, Pest management science.

[5]  Li-xia Xiong,et al.  Synthesis, insecticidal activities and SAR of novel phthalamides targeting calcium channel. , 2014, Bioorganic & medicinal chemistry.

[6]  Li-xia Xiong,et al.  Insecticidal activities of chiral N-trifluoroacetyl sulfilimines as potential ryanodine receptor modulators. , 2014, Journal of agricultural and food chemistry.

[7]  Kai Chen,et al.  Synthesis, insecticidal activity, structure–activity relationship (SAR) and density functional theory (DFT) of novel anthranilic diamides analogs containing 1,3,4-oxadiazole rings , 2014 .

[8]  Jianquan Weng,et al.  Microwave Assistant One Pot Synthesis, Crystal Structure, Antifungal Activities and 3D‐QSAR of Novel 1,2,4‐Triazolo[4,3‐a]pyridines , 2014, Chemical biology & drug design.

[9]  M. Luo,et al.  Novel chlorantraniliprole derivatives as potential insecticides and probe to chlorantraniliprole binding site on ryanodine receptor. , 2014, Bioorganic & medicinal chemistry letters.

[10]  B. Tabashnik,et al.  Defining Terms for Proactive Management of Resistance to Bt Crops and Pesticides , 2014, Journal of economic entomology.

[11]  Li-xia Xiong,et al.  Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing an amino acid methyl ester and their analogues. , 2014, Journal of agricultural and food chemistry.

[12]  Li-xia Xiong,et al.  Synthesis and insecticidal evaluation of novel anthranilic diamides containing N-substitued nitrophenylpyrazole. , 2014, Bioorganic & medicinal chemistry.

[13]  Zhong Li,et al.  Design, synthesis and insecticidal activity of novel anthranilic diamides with benzyl sulfide scaffold , 2013 .

[14]  Li-xia Xiong,et al.  Synthesis, insecticidal activities, and SAR studies of novel pyridylpyrazole acid derivatives based on amide bridge modification of anthranilic diamide insecticides. , 2013, Journal of agricultural and food chemistry.

[15]  Zhong Li,et al.  Pyrrole- and dihydropyrrole-fused neonicotinoids: design, synthesis, and insecticidal evaluation. , 2013, Journal of agricultural and food chemistry.

[16]  Li-xia Xiong,et al.  Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position. , 2013, Bioorganic & medicinal chemistry letters.

[17]  Li-xia Xiong,et al.  Design, Synthesis and Biological Activities of Novel Anthranilic Diamide Insecticide Containing Trifluoroethyl Ether , 2012 .

[18]  Li-xia Xiong,et al.  Synthesis and insecticidal activities of novel anthranilic diamides containing acylthiourea and acylurea. , 2012, Journal of agricultural and food chemistry.

[19]  Bin Hu,et al.  Convenient Chlorination of SomeSpecial Aromatic Compounds Using N-Chlorosuccinimide , 2012 .

[20]  M. Mattos,et al.  Trichloroisocyanuric acid in 98% sulfuric acid: A superelectrophilic medium for chlorination of deactivated arenes , 2011 .

[21]  Li-xia Xiong,et al.  Synthesis and insecticidal activities of novel anthranilic diamides containing modified N-pyridylpyrazoles. , 2010, Journal of agricultural and food chemistry.

[22]  D. Fattori,et al.  Electrophilic Bromination of meta-Substituted Anilines with N-Bromosuccin­imide: Regioselectivityand Solvent Effect , 2009 .

[23]  Li-xia Xiong,et al.  Synthesis, Structure and Biological Activities of Some Novel Anthranilic Acid Esters Containing N‐Pyridylpyrazole , 2009 .

[24]  Mark E. Whalon,et al.  Analysis of global pesticide resistance in arthropods. , 2008 .

[25]  T. M. Stevenson,et al.  Rynaxypyr: a new insecticidal anthranilic diamide that acts as a potent and selective ryanodine receptor activator. , 2007, Bioorganic & medicinal chemistry letters.

[26]  T. M. Stevenson,et al.  Insecticidal anthranilic diamides: a new class of potent ryanodine receptor activators. , 2005, Bioorganic & medicinal chemistry letters.

[27]  W. S. Abbott,et al.  A method of computing the effectiveness of an insecticide. 1925. , 1925, Journal of the American Mosquito Control Association.

[28]  A. Forgash.  History, evolution, and consequences of insecticide resistance☆☆☆ , 1984 .