1-(3,3-dimethylbutyl)imidazole-2-carbaldehyde oxime | 1546949-95-4

• 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)imidazole-2-carbaldehyde oxime
• 英文别名: N-[[1-(3,3-dimethylbutyl)imidazol-2-yl]methylidene]hydroxylamine
• CAS: 1546949-95-4
• 化学式: C₁₀H₁₇N₃O
• 分子量: 195.264
• InChiKey: MLRHSBXBQWKAFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3,3-dimethylbutyl)imidazole-2-carbaldehyde oxime 、 碘甲烷 以 硝基甲烷 为溶剂， 以67%的产率得到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
• 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 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1-(3,3-dimethylbutyl)imidazole-2-carbaldehyde oxime
  参考文献：
  名称：

  [EN] CATALYTIC SCAVENGERS OF ORGANOPHOSPHATES TO POTENTIATE BUTYRYLCHOLINESTERASE (BCHE) AS A CATALYTIC BIOSCAVENGER AND METHODS FOR MAKING AND USING THEM
  [FR] PIÉGEURS CATALYTIQUES D'ORGANOPHOSPHATES POUR POTENTIALISER LA BUTYRYLCHOLINESTÉRASE (HBCHE)

  摘要：

  提供了N-烷基咪唑-2-醛肟，包括阳离子咪唑盐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。通过给予本发明的组合物，不活性或结合的hBChE-OP或hAChE-OP被重新激活，完成了OP的催化周转和失活循环；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再激活组织AChE也有助于整体功效。

  公开号：

  WO2015057822A1

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。