- Synthesis process of indoxacarb
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The invention discloses a synthesis process of indoxacarb. The method comprises the following steps: reacting m-chlorobenzaldehyde serving as a raw material with malonic acid to remove monomolecular water and carbon dioxide to generate an intermediate SRCA, performing a hydrogenation reduction on the intermediate SRCA in an autoclave in the presence of a catalyst to obtain an intermediate SRCH, and cyclizing the SRCH by using hydrogen fluoride as a dehydrating agent to obtain the final product indoxacarb. The synthesis process is simple and easy to implement, energy is saved, consumption is reduced, the yield is increased, and good economic and environmental benefits are obtained.
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- Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides
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Indoxacarb, a commercialized oxadiazine insecticide, nearly irreversibly blocks open/inactivated, but not resting sodium channels. The structure-activity relationships showed that the substituents at the position of the chiral atom in the oxadiazine ring are very important to the biological activity of oxadiazine insecticide. Here we synthesized a series of tricyclic oxadiazine 4a-methyl ester derivatives. The chiral atom in the oxadiazine ring has been epimerized and substituted with either pyrethric acid or cinnamic acid derivatives. Benzene ring in the tricyclic moiety was substituted with a chlorine, fluorine, or bromine atom, and nitrogen-linked benzene ring was substituted with a trifluoromethyl or trifluoromethoxy group. Toxicity of these compounds against Spodoptera litura F. was evaluated. Diastereoisomers of most toxic compounds J7 and J9 with pyrethric acid moiety were separated by flash column chromatography. The more polar diastereoisomers, J7-L-Rf and J9-L-Rf, and compounds J24 and J26 with cinnamic acid moiety exhibited highest insecticidal activities. We further used Monte Carlo energy minimizations to dock compound J7 and J24 in the NavMs-based homology model of the open cockroach sodium channel. In the low-energy binding modes, the compound interacted with residues in the inner pore and domain interfaces, which previously were proposed to contribute to receptors of pyrethroids and sodium channel blocker insecticides. Our results define compound J7 and J24 as a potentially useful optimized hit for the development of multiple sites sodium channel blocker or modulator.
- Zhang, Jianqiang,Hao, Wenbo,Zhorov, Boris S.,Dong, Ke,Jiang, Dingxin
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p. 7793 - 7809
(2019/08/01)
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- Oxadiazine cinnamate derivatives as well as preparation method and application thereof
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The invention provides oxadiazine cinnamate derivatives as well as a preparation method and application thereof. The molecular structures of the oxadiazine cinnamate derivatives are shown in a formula(I) described in the description, wherein R1 is hydrogen, halogen, an alkyl group having 1-4 carbon atoms, alkoxy having 1-4 carbon atoms or an amino group; R2 is -CF3, -OCF3 or -OCH2F. The preparation method provided by the invention combines indoxacarb with cinnamic acid so as to obtain the oxadiazine cinnamate derivatives by rationally designing the structure of the indoxacarb; the oxadiazinecinnamate derivatives not only can significantly increase the poisonous activity of prodenia litura, but also has good biological activity against mosquitoes with drug resistance; compared with commercial indoxacarb insecticide, the poisonous activity of the compounds against pests is greatly enhanced, and the biological activity of the compounds for drug-resistant pests is especially enhanced, sothat drug protection is provided for the prevention and control of the resistant pests. Furthermore, the raw materials used in the method for producing the compounds provided by invention are readilyavailable, the reaction conditions are mild, and the yield of the target product is high.
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- Oxadiazine derivative, and preparation method and application thereof
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The invention discloses an oxadiazine derivative, and a preparation method and an application thereof. The oxadiazine derivative has a molecular structure as shown in a formula (I) described in the specification. The invention provides the preparation method of the oxadiazine derivative, and the application of the oxadiazine derivative in preparation of pesticides used for prevention and treatment of agricultural or sanitary pests or in preparation of pharmaceutical preparations used for prevention and treatment of animal parasites. The oxadiazine derivative provided by the invention contains two pharmacophores with different action modes to insect sodium ion channels, can reach the purpose of synergistic interaction, shows higher biological activity to pests, can achieve the purpose of increasing prevention and treatment spectrum, and has broad application prospects.
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- Design, synthesis and structure-activity relationship of indoxacarb analogs as voltage-gated sodium channel blocker
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Indoxacarb, the first commercialized pyrazoline-type sodium-channel blocker, is a commonly used insecticide because of high selectivity. To discover sodium-channel blocker with high insecticidal activity, a series of novel indoxacarb analogs were designed and synthesized by judicious structural modifications of the substituent group of C5, C6 in indenone and C′4 in benzene ring. Some analogs exhibited significant insecticidal activities against Spodoptera litura F. and excellent BgNav1-1a channel inhibitory activity. The structure-activity analysis indicated that the presence of strong electron-withdrawing group and decreased steric hindrance of indenone ring (R1, R2) in 5- and 6-position could enhance larvicidal activity and BgNav1-1a channel inhibitory activity.
- Hao, Wenbo,Fu, Chunling,Yu, Huijuan,Chen, Jian,Xu, Hanhong,Shao, Guang,Jiang, Dingxin
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supporting information
p. 4576 - 4579
(2015/10/12)
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- The discovery of indoxacarb: Oxadiazines as a new class of pyrazoline-type insecticides
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The evolution of the insecticidal pyrazoline moiety that was originally discovered in 1972 has led to the discovery of a new crop insecticide, indoxacarb, which is the first commercialized pyrazoline-type sodium-channel blocker. Both monocyclic and fused-tricyclic pyrazolines and pyridazines, as well as structurally related semicarbazones were examined prior to the discovery of analogous tricyclic oxadiazines which had similarly high activity as well as favorable environmental dissipation rates and low toxicity to non-target organisms. The eventual leading candidate, DPX-JW062, was originally obtained as a racemic molecule, but a chiral synthesis was developed which produces material that is 50% ee in the insecticidal (+)-S-enantiomer (DPX-MP062, indoxacarb).
- McCann, Stephen F.,Annis, Gary D.,Shapiro, Rafael,Piotrowski, David W.,Lahm, George P.,Long, Jeffery K.,Lee, Kevin C.,Hughes, Margaret M.,Myers, Brian J.,Griswold, Sandra M.,Reeves, Bonita M.,March, Robert W.,Sharpe, Paula L.,Lowder, Patrick,Barnette, William E.,Wing, Keith D.
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p. 153 - 164
(2007/10/03)
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