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用原位点击化学方法合成新型乙酰胆碱抑制剂 被引量：1

Synthesis of the novel acetylcholinesterase inhibitors by in situ click chemistry
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摘要 采用高效液相色谱-质谱联用技术,分析加入叠氮和炔构建块的乙酰胆碱酯酶(AChE)孵育液。找到4个乙酰胆碱酯酶诱导叠氮和炔构建块发生Husigen[3+2]环加成反应的产物,然后通过常规化学合成及活性筛选证明该4种产物(syn-TZ2/QA5、syn-6TZ2/QA5、syn-8TZ2/QA5和syn-6TZ2/BA6)具有很强的乙酰胆碱酯酶抑制活性。 The solutions of electrophorus AChE with the building blocks were injected directly into the LC/MSD instrument to perform LC/MS-SIM analysis.Then four cycloaddition products were indentified by their retention times and molecular weights.In order to determine the feasibility of the result of in situ click chemistry,the products were synthesized by the conventional click chemistry.The preliminary bioassay showed that all of them exhibited better AChE（electrophorus） inhibitory activity.
作者 郭永彪 刘海波 许明
机构地区 防化研究院
出处 《现代仪器》 2012年第3期43-46,共4页 Modern Instruments
关键词 液相色谱-质谱 原位点击化学 乙酰胆碱酯酶抑制剂 Liquid chromatography–mass spectrometry In situ click chemistry Acetylcholinesterase inhibitors
分类号 O657.7 [理学—分析化学]
  • 相关文献

参考文献6

  • 1Lewis W G, Green L G, Grynszpan F et al. Click chemistry in situ: acetylcholinesterase as a aeaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks, Angew. Chem. Int. Ed, 2002, 41:1053-1057.
  • 2Manetsch R, Krasinski A, Radic Z et al. In situ click chemistry: enzyme inhibitors made to their own specifications, J. Am. Chem. Soc, 2004, 126:12809-12818.
  • 3Krasiski A, Radi Z, Manetsch R, et al. In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitors, J. Am. Chem. Soc, 2005, 127: 6686-6692.
  • 4Bourne Y, Kolb H C, Radic Z et al. Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation, Natl. Acad. Sci. U.S.A, 2004, 101:1449-1454.
  • 5郭永彪,刘海波,许明.用“点击化学”法合成新型他克林-四氢异喹啉异二联体[J].合成化学,2011,19(3):299-303. 被引量：2
  • 6郭永彪.原位点击化学在乙酰胆碱酯酶抑制剂合成中的应用.北京:防化研究院,2011.

二级参考文献14

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  • 5Manetsch R, Krasinski A, Radic Z, et al. In situ click chemistry:Enzyme inhibitors made to their own specifications [ J ]. J Am Chem Soc, 2004, 126: 12809 - 12818.
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共引文献1

同被引文献19

  • 1Kolb H C, Finn M G, Sharpless K B. Click chemistry: di verse chemical function from a few good reactions[J]. An- gew Chem Int Ed,2001,40(11) :2 004-2 021.
  • 2Van Dijk M, Rijkers D T S, Liskamp R M J, et al. Synthesis and applications of biomedical and pharmaceutical polymers via click chemistry methodologies[J]. Bioconjugate Chem, 2009,20 (II) :2 001-2 016.
  • 3Shoichet M S. Polymer scaffolds for biomaterials applica- tions[J]. Macromolecules, 2010,4,3(2) : 581-591.
  • 4Zhang G Y, Liu J, Yang Q Z, et al. Disulfide-containing brushed polyethylenimine derivative synthesized by click chemistry for nonviral gene delivery [J ]. Bioconjugate Chem,2012,23(6):-1 290-1 299.
  • 5Deng J J,Zhou Y F,Xu B,et al. Dendronized chitosan deriv- ative as a biocompatible gene delivery carrier[J]. Biomacro molecules, 2011,12(3) : 642-649.
  • 6Gao Y,Zhang Z W,Chen L L,et al. Synthesis of 6-N,N,N- trimethyltriazole chitosan via "click chemistry" and evalua- tion for gene delivery[J]. Biomacromolecules, 2009,10 (8) 2 175-2 182.
  • 7Talelli M, Morita K, Rijcken C J F, et al. Synthesis and characterization of biodegradable and thermosensitive poly- meric micelles With covalently bound doxorubicin-glucu-ronide prodrug via click chemistr[J]. Bioconjugate Chem, 2011,22(12):2 519-2 530.
  • 8Garg S M, Xiong X B, Lu C H, et al. Application of click chemistry in the preparation of poly(ethyleneoxide)-block poly(--caprolactone) with hydrolyzable cross-links in the micellar core[J]. Macromolecules, 2011,44, (7) : 2 058 2 066.
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  • 10Li J,Zheng M,Jiang H, et al. Syntheses of triazole-modified zanamivir analogues via click chemistry and anti AIV activi- ties[J]. Bioorg Med Chem Lett, 2006, 16 (19): 5 009 5 013.

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现代仪器
2012年 第3期

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