2-(hydroxyimino)-N,N-dimethyl-N'-propylacetimidamide hydrochloride | 1293993-43-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(hydroxyimino)-N,N-dimethyl-N'-propylacetimidamide hydrochloride
• 英文别名: 2-hydroxyimino-N,N-dimethyl-N'-propylethanimidamide;hydrochloride
• CAS: 1293993-43-7
• 化学式: C₇H₁₅N₃O*ClH
• 分子量: 193.677
• InChiKey: COUCQLIUNAFHGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.24
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  48.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl 2-(benzyloxyimino)-N-propylethanimidothioate trifluoromethanesulfonate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 5.0h， 生成 2-(hydroxyimino)-N,N-dimethyl-N'-propylacetimidamide hydrochloride
  参考文献：
  名称：

  Amidine−Oximes: Reactivators for Organophosphate Exposure

  摘要：

  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.

  DOI：

  10.1021/jm200054r

文献信息

• [EN] BLOOD BRAIN BARRIER-PENETRATING OXIMES FOR CHOLISTENERASES REACTIVATION<br/>[FR] OXIMES FRANCHISSANT LA BARRIÈRE HÉMATO-ENCÉPHALIQUE POUR RÉACTIVER DES CHOLINESTÉRASES
  申请人：HUMAN BIOMOLECULAR RES INST

  公开号：WO2012083261A1

  公开（公告）日：2012-06-21

  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。