1-(3,3-dimethylbutyl)-2-((hydroxyimino)methyl)-3-methyl-imidazol-3-ium iodide | 1546950-17-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3,3-dimethylbutyl)-2-((hydroxyimino)methyl)-3-methyl-imidazol-3-ium iodide
• 英文别名: N-[[1-(3,3-dimethylbutyl)-3-methylimidazol-3-ium-2-yl]methylidene]hydroxylamine;iodide
• CAS: 1546950-17-7
• 化学式: C₁₁H₂₀N₃O*I
• 分子量: 337.204
• InChiKey: GOIZHCLEGNAHGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.44
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  41.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,3-二甲基-1-溴丁烷 [1647-23-0] 在 盐酸羟胺 、 sodium carbonate 、 potassium carbonate 作用下， 以 硝基甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1-(3,3-dimethylbutyl)-2-((hydroxyimino)methyl)-3-methyl-imidazol-3-ium iodide
  参考文献：
  名称：

  Imidazole Aldoximes Effective in Assisting Butyrylcholinesterase Catalysis of Organophosphate Detoxification

  摘要：

  Intoxication by organophosphate (OP) nerve agents and pesticides should be addressed by efficient, quickly deployable countermeasures such as antidotes reactivating acetylcholinesterase or scavenging the parent OP. We present here synthesis and initial in vitro characterization of 14 imidazole aldoximes and their structural refinement into three efficient reactivators of human butyrylcholinesterase (hBChE) inhibited covalently by nerve agent OPs, sarin, cyclosarin, VX, and the OP pesticide metabolite, paraoxon. Rapid reactivation of OP-hBChE conjugates by uncharged and nonprotonated tertiary imidazole aldoximes allows the design of a new OP countermeasure by conversion of hBChE from a stoichiometric to catalytic OP bioscavenger with the prospect of oral bioavailability and central nervous system penetration. The enhanced in vitro reactivation efficacy determined for tertiary imidazole aldoximes compared to that of their quaternary N-methyl imidazolium analogues is attributed to ion pairing of the cationic imidazolium with Asp 70, altering a reactive alignment of the aldoxime with the phosphorus in the OP-hBChE conjugate.

  DOI：

  10.1021/jm401650z

文献信息

• CATALYTIC SCAVENGERS OF ORGANOPHOSPHATES TO POTENTIATE BUTYRYLCHOLINESTERASE (hBChE) AS A CATALYTIC BIOSCAVENGER AND METHODS FOR MAKING AND USING THEM
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20160256438A1

  公开（公告）日：2016-09-08

  Provided are N-alkyl imidazole 2-aldoximes, including cationic imidazolium and uncharged tertiary imidazole aldoximes, and compositions and methods for making and using them, including methods for reactivating human butyrylcholinesterase (hBChE) or acetylcholinesterase (hAChE) inhibited by organophosphate (OP). By administration of a composition of the invention, the inactive or conjugated hBChE-OP or hAChE-OP is reactivated and the catalytic cycle of turnover and inactivation of the OP is completed; and in alternative embodiments, secondary mechanisms of reversible protection of hBChE and hAChE from irreversible inactivation by OPs and reactivation of tissue AChE also contribute to overall efficacy.

  提供了N-烷基咪唑-2-醛肟，包括阳离子咪唑和不带电的三级咪唑醛肟，以及制备和使用它们的组合物和方法，包括重新激活被有机磷酸酯（OP）抑制的人丁酰胆碱酯酶（hBChE）或乙酰胆碱酯酶（hAChE）的方法。通过使用本发明的组合物，不活性或结合的hBChE-OP或hAChE-OP被重新激活，完成OP的催化循环和失活；在替代实施方案中，可逆保护hBChE和hAChE免受OP不可逆失活的次要机制以及组织AChE的重新激活也有助于总体功效。
• Catalytic scavengers of organophosphates to potentiate butyrylcholinesterase (hBChE) as a catalytic bioscavenger and methods for making and using them
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10172831B2

  公开（公告）日：2019-01-08

  Provided are N-alkyl imidazole 2-aldoximes, including cationic imidazolium and uncharged tertiary imidazole aldoximes, and compositions and methods for making and using them, including methods for reactivating human butyrylcholinesterase (hBChE) or acetylcholinesterase (hAChE) inhibited by organophosphate (OP). By administration of a composition of the invention, the inactive or conjugated hBChE-OP or hAChE-OP is reactivated and the catalytic cycle of turnover and inactivation of the OP is completed; and in alternative embodiments, secondary mechanisms of reversible protection of hBChE and hAChE from irreversible inactivation by OPs and reactivation of tissue AChE also contribute to overall efficacy.

  本发明提供了N-烷基咪唑2-醛肟，包括阳离子咪唑鎓和不带电的叔咪唑醛肟，以及制造和使用它们的组合物和方法，包括重新激活被有机磷（OP）抑制的人丁酰胆碱酯酶（hBChE）或乙酰胆碱酯酶（hAChE）的方法。通过施用本发明的组合物，无活性或共轭的 hBChE-OP 或 hAChE-OP 被重新激活，OP 的周转和失活催化循环完成；在另一个实施方案中，可逆保护 hBChE 和 hAChE 免受 OP 的不可逆失活以及重新激活组织 AChE 的次级机制也有助于提高整体疗效。
• Imidazole Aldoximes Effective in Assisting Butyrylcholinesterase Catalysis of Organophosphate Detoxification
  作者：Rakesh K. Sit、Valery V. Fokin、Gabriel Amitai、K. Barry Sharpless、Palmer Taylor、Zoran Radić

  DOI：10.1021/jm401650z

  日期：2014.2.27

  Intoxication by organophosphate (OP) nerve agents and pesticides should be addressed by efficient, quickly deployable countermeasures such as antidotes reactivating acetylcholinesterase or scavenging the parent OP. We present here synthesis and initial in vitro characterization of 14 imidazole aldoximes and their structural refinement into three efficient reactivators of human butyrylcholinesterase (hBChE) inhibited covalently by nerve agent OPs, sarin, cyclosarin, VX, and the OP pesticide metabolite, paraoxon. Rapid reactivation of OP-hBChE conjugates by uncharged and nonprotonated tertiary imidazole aldoximes allows the design of a new OP countermeasure by conversion of hBChE from a stoichiometric to catalytic OP bioscavenger with the prospect of oral bioavailability and central nervous system penetration. The enhanced in vitro reactivation efficacy determined for tertiary imidazole aldoximes compared to that of their quaternary N-methyl imidazolium analogues is attributed to ion pairing of the cationic imidazolium with Asp 70, altering a reactive alignment of the aldoxime with the phosphorus in the OP-hBChE conjugate.