ethyl 2-(4-methoxybenzyloxyimino)acetate | 1293993-63-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl 2-(4-methoxybenzyloxyimino)acetate
• 英文别名: ethyl 2-[(4-methoxyphenyl)methoxyimino]acetate
• CAS: 1293993-63-1
• 化学式: C₁₂H₁₅NO₄
• 分子量: 237.255
• InChiKey: DHNQRWIDXXDWCT-UHFFFAOYSA-N

物化性质

• 沸点：
  338.6±44.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-methoxybenzyloxyimino)acetate 在 劳森试剂 、 三甲基铝 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 1.0h， 生成 2-(4-methoxybenzyloxyimino)-N-phenylethanethioamide
  参考文献：
  名称：

  Nonquaternary Reactivators for Organophosphate-Inhibited Cholinesterases

  摘要：

  A new class of amidine-oxime reactivators of organophosphate (OP)-inhibited cholinesterases (ChE) was synthesized and tested in vitro and in vivo. Compared with 2-PAM, the most promising cyclic amidine-oxime (i.e., 12e) showed comparable or greater reactivation of OP-inactivated AChE and OP-inactivated BChE. To the best of our knowledge, this is the first report of a nonquaternary oxime that has, comparable to 2-PAM, in vitro potency for reactivation of Sarin (GB)-inhibited AChE and BChE. Amidine-oximes were tested in vitro, and reactivation rates for OP-inactivated butyrylcholinesterase (BChE) were greater than those for 2-PAM or MINA. Amidine-oxime reactivation rates for OP-inactivated acetylcholinesterase (AChE) were lower compared to 2-PAM but greater compared with MINA. Amidine-oximes were tested in vivo for protection against the toxicity of nerve agent model compounds. (i.e., a model of Sarin). Post-treatment (i.e., 5 min after OP exposure, i.p,) with amidine oximes 7a-c and 12a, 12c, 12e, 12f, and 15b (145 mu mol/kg, i.p.) protected 100% of the mice challenged with the satin model compound. Even at 25% of the initial dose of amidine-oxime (i.e., a dose of 36 mu mol/kg, i.p.), 7b and 12e protected 100% of the animals challenged with the sarin nerve agent model compound that caused lethality in 6/11 animals without amidine-oxime.

  DOI：

  10.1021/jm201364d
• 作为产物：
  描述：

  ethyl 2-(hydroxyimino)acetate 、 4-甲氧基氯苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以72%的产率得到ethyl 2-(4-methoxybenzyloxyimino)acetate
  参考文献：
  名称：

  [EN] BLOOD BRAIN BARRIER-PENETRATING OXIMES FOR CHOLISTENERASES REACTIVATION
  [FR] OXIMES FRANCHISSANT LA BARRIÈRE HÉMATO-ENCÉPHALIQUE POUR RÉACTIVER DES CHOLINESTÉRASES

  摘要：

  该发明描述了一种能够穿越血脑屏障的药物，可以保护免受有机磷杀虫剂、神经毒剂或其他亲电性物质的侵害，通过重新激活被抑制的胆碱酯酶（即乙酰胆碱酯酶和丁酰胆碱酯酶）以及其他蛋白质在外周和中枢神经系统中的作用。

  公开号：

  WO2012083261A1

文献信息

• BLOOD BRAIN BARRIER-PENETRATING OXIMES FOR CHOLISTENERASES REACTIVATION
  申请人：Cashman John R.

  公开号：US20140051712A1

  公开（公告）日：2014-02-20

  The invention describes pharmaceutical agents capable of crossing the blood brain barrier to protect against organophosphate pesticides and nerve agents or other electrophiles by reactivating inhibited cholinesterase (i.e., acetylcholinesterase and butyrylcholinesterase) and other proteins in the peripheral and central nervous system.

  该发明描述了一种药物，能够穿过血脑屏障，保护免受有机磷杀虫剂和神经毒剂或其他电子亲合剂的损害，通过重新激活抑制的胆碱酯酶（即乙酰胆碱酯酶和丁酰胆碱酯酶）和其他蛋白质在中枢和周围神经系统中发挥作用。
• Amidine−Oximes: Reactivators for Organophosphate Exposure
  作者：Jarosław Kalisiak、Erik C. Ralph、Jun Zhang、John R. Cashman

  DOI：10.1021/jm200054r

  日期：2011.5.12

  A new class of amidine-oxime reactivators of organophosphate (OP)-inhibited cholinesterases (ChE) were designed, synthesized, and tested. These compounds represent a novel group of oximes with enhanced capabilities of crossing the blood-brain barrier. Lack of brain penetration is a major limitation for currently used oximes as antidotes of OP poisoning. The concept described herein relies on a combination of an amidine residue and oxime functionality whereby the amidine increases the binding affinity to the ChE and the oxime is responsible for reactivation. Amidine-oximes were tested in vitro and reactivation rates for OP-BuChE were greater than pralidoxime (2-PAM) or monoisonitrosoacetone (MINA). Amidine-oxime reactivation rates for OP-AChE were lower compared to 2-PAM but greater compared with MINA. After pretreatment for 30 min with oximes 15c and 15d (145 mu mol/kg, ip) mice were challenged with a soman model compound. In addition, 15d was tested in a post-treatment experiment (145 mu mol/kg, ip, administration 5 min after sarin model compound exposure). In both cases, amidine-oximes afforded 100% 24 h survival in an animal model of OP exposure.