ethyl 2-(hydroxyimino)-2-(methylanilino)acetate | 850131-48-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-(hydroxyimino)-2-(methylanilino)acetate
• 英文别名: ethyl 2-hydroxyimino-2-(N-methylanilino)acetate
• CAS: 850131-48-5
• 化学式: C₁₁H₁₄N₂O₃
• 分子量: 222.244
• InChiKey: WMHQCIYJSPMHBS-UHFFFAOYSA-N

物化性质

• 熔点：
  101-103 °C(Solv: dichloromethane (75-09-2); hexane (110-54-3))
• 沸点：
  339.3±25.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.47
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  62.13
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-(3-氨基丙基)吡咯烷 、 ethyl 2-(hydroxyimino)-2-(methylanilino)acetate 以 乙醇 为溶剂， 生成 RS166C
  参考文献：
  名称：

  New Structural Scaffolds for Centrally Acting Oxime Reactivators of Phosphylated Cholinesterases

  摘要：

  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.

  DOI：

  10.1074/jbc.m111.230656
• 作为产物：
  描述：

  氯代肟基乙酸乙酯 、 N-甲基苯胺 在 三乙胺 作用下， 以 乙醚 为溶剂， 反应 1.5h， 以75%的产率得到ethyl 2-(hydroxyimino)-2-(methylanilino)acetate
  参考文献：
  名称：

  An Easy Transformation of 2-Amino-2-(hydroxyimino)acetates to Carbamoylformamidoximes

  摘要：

  氨基甲酰基甲酰胺肟 5 由 2-氨基-2-（羟基亚氨基）乙酸酯 3 与氨基溴化镁 4 反应合成，后者由胺 2 和乙基溴化镁原位制备。

  DOI：

  10.1055/s-2004-837285

文献信息

• An Easy Transformation of 2-Amino-2-(hydroxyimino)acetates to Carbamoylformamidoximes
  作者：Demetrios N. Nicolaides、Konstantinos E. Litinas、Theodora Papamehael、Hanna Grzeskowiak、Daman R. Gautam、Konstantina C. Fylaktakidou

  DOI：10.1055/s-2004-837285

  日期：——

  Carbamoylformamidoximes 5 are synthesized from 2-amino-2-(hydroxyimino)acetates 3 by reaction with aminomagnesium bromides 4, prepared in situ from amines 2 and ethylmagnesium bromide.

  氨基甲酰基甲酰胺肟 5 由 2-氨基-2-（羟基亚氨基）乙酸酯 3 与氨基溴化镁 4 反应合成，后者由胺 2 和乙基溴化镁原位制备。
• 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.