RS-113B | 1313032-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: RS-113B
• 英文别名: RS113B
• CAS: 1313032-16-4
• 化学式: C₉H₁₅N₃O
• 分子量: 181.238
• InChiKey: UHEVHGWQQBMZGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 重原子数：
  13.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  50.41
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  RS-113B 、 三氟甲烷磺酸甲酯 以 硝基甲烷 为溶剂， 以60%的产率得到2-((hydroxyimino)methyl)-3-methyl-1-pentyl-imidazol-3-ium trifluoromethanesulfonate
  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
• 作为产物：
  描述：

  1-碘戊烷 在 盐酸羟胺 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 RS-113B
  参考文献：
  名称：

  咪唑鎓醛肟作为沙林和VX抑制人乙酰胆碱酯酶（h AChE）的活化剂的合成及体外活化筛选

  摘要：

  有机磷酸盐（OP）中毒的后处理涉及使用肟活化剂作为解毒剂。广泛研究了结构不同的肟，以检查它们对OP抑制的胆碱酯酶的动力学和机理行为。合成了一系列结构上相关的1,3-二取代-2-[（羟基亚氨基甲基）烷基]咪唑鎓卤化物（5a-5e，9a-9c），并进一步评估了它们的体外再活化能力以重新活化被沙林和VX抑制的物质。人乙酰胆碱酯酶（h AChE）。将观察到的结果与标准活化剂的活化效率进行了比较。2-PAM，obidoxime和HI-6。在合成的肟中，5a，9a和9b在VX的情况下，仅9a表现出与2-PAM相当的反应性，而被发现是对抗沙林抑制的h AChE的最有效的活化剂。吡啶鎓环与咪唑环的结合导致所制备的活化剂的活化强度大大提高。合成的活化剂的理化性质也得到了评估。

  DOI：

  10.1016/j.cbi.2016.04.034

文献信息

• New Structural Scaffolds for Centrally Acting Oxime Reactivators of Phosphylated Cholinesterases
  作者：Rakesh K. Sit、Zoran Radić、Valeria Gerardi、Limin Zhang、Edzna Garcia、Maja Katalinić、Gabriel Amitai、Zrinka Kovarik、Valery V. Fokin、K. Barry Sharpless、Palmer Taylor

  DOI：10.1074/jbc.m111.230656

  日期：2011.6

  We describe here the synthesis and activity of a new series of oxime reactivators of cholinesterases (ChEs) that contain tertiary amine or imidazole protonatable functional groups. Equilibration between the neutral and protonated species at physiological pH enables the reactivators to cross the blood-brain barrier and distribute in the CNS aqueous space as dictated by interstitial and cellular pH values. Our structure-activity analysis of 134 novel compounds considers primarily imidazole aldoximes and N-substituted 2-hydroxyiminoacetamides. Reactivation capacities of novel oximes are rank ordered by their relative reactivation rate constants at 0.67 mM compared with 2-pyridinealdoxime methiodide for reactivation of four organophosphate (sarin, cyclosarin, VX, and paraoxon) conjugates of human acetylcholinesterase (hAChE). Rank order of the rates differs for reactivation of human butyrylcholinesterase (hBChE) conjugates. The 10 best reactivating oximes, predominantly hydroxyimino acetamide derivatives (for hAChE) and imidazole-containing aldoximes (for hBChE) also exhibited reasonable activity in the reactivation of tabun conjugates. Reactivation kinetics of the lead hydroxyimino acetamide reactivator of hAChE, when analyzed in terms of apparent affinity (1/K-ox) and maximum reactivation rate (k(2)), is superior to the reference uncharged reactivators monoisonitrosoacetone and 2,3-butanedione monoxime and shows potential for further refinement. The disparate pH dependences for reactivation of ChE and the general base-catalyzed oximolysis of acetylthiocholine reveal that distinct reactivator ionization states are involved in the reactivation of ChE conjugates and in conferring nucleophilic reactivity of the oxime group.
• 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.