methyl 2,2-diethoxy-N-methylethanimidothioate trifluoromethanesulfonate | 1331832-18-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: methyl 2,2-diethoxy-N-methylethanimidothioate trifluoromethanesulfonate
• 英文别名: methyl 2,2-diethoxy-N-methylethanimidothioate;trifluoromethanesulfonic acid
• CAS: 1331832-18-8
• 化学式: CHF₃O₃S*C₈H₁₇NO₂S
• 分子量: 341.373
• InChiKey: MLYFYZFHIAIAJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.17
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 2,2-diethoxy-N-methylethanimidothioate trifluoromethanesulfonate 在 ion-exchange resin IRA-400 (Cl) 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 2,2-diethoxy-N,N,N'-trimethylacetimidamide 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
• 作为产物：
  描述：

  2,2-diethoxy-N-methylacetamide 在 劳森试剂 作用下， 以 四氢呋喃 、 硝基甲烷 为溶剂， 反应 2.0h， 生成 methyl 2,2-diethoxy-N-methylethanimidothioate trifluoromethanesulfonate
  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

• 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.