O-2-fluoroethyl-O-p-nitrophenyl methyphosphonothionate | 889-14-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: O-2-fluoroethyl-O-p-nitrophenyl methyphosphonothionate
• 英文别名: methyl-thiophosphonic acid O-(2-fluoro-ethyl ester)-O'-(4-nitro-phenyl ester)；Methyl-thiophosphonsaeure-O-(2-fluor-aethylester)-O'-(4-nitro-phenylester)；Phosphonothioic acid, methyl-, O-(2-fluoroethyl) O-(p-nitrophenyl) ester；2-fluoroethoxy-methyl-(4-nitrophenoxy)-sulfanylidene-λ5-phosphane
• CAS: 889-14-5
• 化学式: C₉H₁₁FNO₄PS
• 分子量: 279.229
• InChiKey: ISVKKUJXLMPXMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  96.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O-2-fluoroethyl-O-p-nitrophenyl methyphosphonothionate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 1-Fluoro-2-[fluoro(methyl)phosphoryl]oxyethane 、 2-fluoroethyl 4-nitrophenyl methylphosphonate
  参考文献：
  名称：

  Synthesis and anti-acetylcholinesterase properties of novel β- and γ-substituted alkoxy organophosphonates

  摘要：

  Activated organophosphate (OP) insecticides and chemical agents inhibit acetylcholinesterase (AChE) to form OP-AChE adducts. Whereas the structure of the OP correlates with the rate of inhibition, the structure of the OP-AChE adduct influences the rate at which post-inhibitory reactivation or aging phenomena occurs. In this report, we prepared a panel of beta-substituted ethoxy and gamma-substituted propoxy phosphonoesters of the type p-NO2PhO-P(X)(R)[(O(CH2)(n)Z] (R = Me, Et; X = O, S; n = 2, 3; Z = halogen, OTs) and examined the inhibition of three AChEs by select structures in the panel. The beta-fluoroethoxy methylphosphonate analog (R = Me, Z = F, n = 2) was the most potent anti-AChE compound comparable (k(i); similar to 6 x 10(6) M-1 min(-1)) to paraoxon against EEAChE. Analogs with Z = Br, I, or OTs were weak inhibitors of the AChEs, and methyl phosphonates (R = Me) were more potent than the corresponding ethyl phosphonates (R = Et). As expected, analogs with a thionate linkage (P=S) were poor inhibitors of the AChEs. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.010
• 作为产物：
  描述：

  2-fluoroethyl 4-nitrophenyl methylphosphonate 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以64%的产率得到O-2-fluoroethyl-O-p-nitrophenyl methyphosphonothionate
  参考文献：
  名称：

  Cholinesterase Inhibitors

  摘要：

  该发明提供了抑制胆碱酯酶的化合物，例如乙酰胆碱酯酶和丁酰胆碱酯酶。这些化合物可用于预防或治疗患者（例如人类）暴露于有机磷神经毒剂（例如沙林和VX）或治疗患有神经退行性疾病（如阿尔茨海默病或路易体痴呆症）的患者。这些化合物还可作为诊断工具用于医学或研究放射学（例如正电子发射断层扫描）时，当与放射性核素（例如[18F]）合成时。还提供了用于合成这些化合物的合成方案。

  公开号：

  US20130343994A1

文献信息

• Cholinesterase Inhibitors
  申请人：Thompson Charles M.

  公开号：US20130343994A1

  公开（公告）日：2013-12-26

  The invention provides compounds that inhibit cholinesterases, such as acetylcholinesterase and butyrylcholinesterase. Such compounds are useful to prevent or treat exposure of a patient (e.g., a human) to an organophosphoric nerve agent (e.g., sarin and VX) or to treat a patient suffering from a neurodegenerative disorder such as Alzheimer's Disease or Lewy Body Dementia. The compounds are further useful as diagnostic tools for use in medical or research radiography (e.g., positron emission tomography) when synthesized with a radionuclide (e.g., [18F]. Synthetic schemes to produce such compounds are also provided.

  该发明提供了抑制胆碱酯酶的化合物，例如乙酰胆碱酯酶和丁酰胆碱酯酶。这些化合物可用于预防或治疗患者（例如人类）暴露于有机磷神经毒剂（例如沙林和VX）或治疗患有神经退行性疾病（如阿尔茨海默病或路易体痴呆症）的患者。这些化合物还可作为诊断工具用于医学或研究放射学（例如正电子发射断层扫描）时，当与放射性核素（例如[18F]）合成时。还提供了用于合成这些化合物的合成方案。
• Kabatschnik et al., Zhurnal Obshchei Khimii, 1959, vol. 29, p. 1671,1678;engl.Ausg.S.1647,1653
  作者：Kabatschnik et al.

  DOI：——

  日期：——
• Synthesis and anti-acetylcholinesterase properties of novel β- and γ-substituted alkoxy organophosphonates
  作者：S. Kaleem Ahmed、Yamina Belabassi、Lakshmi Sankaranarayanan、Chih-Kai Chao、John M. Gerdes、Charles M. Thompson

  DOI：10.1016/j.bmcl.2013.02.010

  日期：2013.4

  Activated organophosphate (OP) insecticides and chemical agents inhibit acetylcholinesterase (AChE) to form OP-AChE adducts. Whereas the structure of the OP correlates with the rate of inhibition, the structure of the OP-AChE adduct influences the rate at which post-inhibitory reactivation or aging phenomena occurs. In this report, we prepared a panel of beta-substituted ethoxy and gamma-substituted propoxy phosphonoesters of the type p-NO2PhO-P(X)(R)[(O(CH2)(n)Z] (R = Me, Et; X = O, S; n = 2, 3; Z = halogen, OTs) and examined the inhibition of three AChEs by select structures in the panel. The beta-fluoroethoxy methylphosphonate analog (R = Me, Z = F, n = 2) was the most potent anti-AChE compound comparable (k(i); similar to 6 x 10(6) M-1 min(-1)) to paraoxon against EEAChE. Analogs with Z = Br, I, or OTs were weak inhibitors of the AChEs, and methyl phosphonates (R = Me) were more potent than the corresponding ethyl phosphonates (R = Et). As expected, analogs with a thionate linkage (P=S) were poor inhibitors of the AChEs. (C) 2013 Elsevier Ltd. All rights reserved.