1-(3-bromopropyl)-4-(hydroxyiminomethyl)pyridinium bromide | 6602-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(3-bromopropyl)-4-(hydroxyiminomethyl)pyridinium bromide
• 英文别名: (NZ)-N-[[1-(3-bromopropyl)pyridin-1-ium-4-yl]methylidene]hydroxylamine;bromide
• CAS: 6602-22-8
• 化学式: Br*C₉H₁₂BrN₂O
• 分子量: 324.015
• InChiKey: UJBDZNKJLCYPPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.43
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  36.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异喹啉 、 1-(3-bromopropyl)-4-(hydroxyiminomethyl)pyridinium bromide 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以75%的产率得到4-hydroxyiminomethyl-1,10-(prop-1,3-diyl)-1-pyridinium-1'-isoquinolinium dibromide
  参考文献：
  名称：

  Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage—Preparation, in vitro screening and molecular docking

  摘要：

  The treatment of organophosphorus (OP) poisoning consists of the administration of a parasympatholytic agent (e. g., atropine), an anticonvulsant (e. g., diazepam) and an acetylcholinesterase (AChE) reactivator (e. g., obidoxime). The AChE reactivator is the causal treatment of OP exposure, because it cleaves the OP moiety covalently bound to the AChE active site. In this paper, fourteen novel AChE reactivators are described. Their design originated from a former promising compound K027. These compounds were synthesized, evaluated in vitro on human AChE (hAChE) inhibited by tabun, paraoxon, methylparaoxon and DFP and then compared to commercial hAChE reactivators (pralidoxime, HI-6, trimedoxime, obidoxime, methoxime) or previously prepared compounds (K027, K203). Three of these novel compounds showed a promising ability to reactivate hAChE comparable or better than the used standards. Consequently, a molecular docking study was performed for three of these promising novel compounds. The docking results confirmed the apparent influence of pi-pi or cation -pi interactions and hydrogen bonding for reactivator binding within the hAChE active site cleft. The SAR features concerning the non-oxime part of the reactivator molecule are also discussed. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.021
• 作为产物：
  描述：

  4-吡啶甲醛 在 sodium hydroxide 作用下， 以 氯仿 、 水 为溶剂， 反应 84.0h， 生成 1-(3-bromopropyl)-4-(hydroxyiminomethyl)pyridinium bromide
  参考文献：
  名称：

  Novel pyridinium oximes: synthesis, molecular docking and in vitro reactivation studies

  摘要：

  一种计算方法已尝试用于筛选基于4-吡哆醇铵（4P）环的再生剂，以恢复被对硫磷磷酸酯酶抑制的AChE的活性。

  DOI：

  10.1039/c4ra14696d

文献信息

• Quaternary salts of 4,3′ and 4,4′ bis-pyridinium monooximes: Synthesis and biological activity
  作者：Srinivas Rao Chennamaneni、Venkateswarlu Vobalaboina、Achaiah Garlapati

  DOI：10.1016/j.bmcl.2005.04.026

  日期：2005.6

  pyridinium)pentane were synthesized and characterized by spectral data. Their ability to reactivate tetraethyl pyrophosphate inhibited mouse total brain cholinesterase was investigated and compared with 2-pyridine aldoxime chloride (2-PAM). All the compounds were found to be more effective acetylcholinesterase reactivators when compared with the conventional oxime, 2-PAM, except the compound (5a) with pentylene

  六个不对称的双季一元肟即。1-（4-羟基亚氨基甲基吡啶鎓）-3-（3 / 4-氨基甲酰基吡啶鎓）丙烷，1-（4-羟基亚氨基甲基吡啶鎓）-4-（3 / 4-氨基甲酰基吡啶鎓）丁烷，1-（4-羟基亚氨基甲基）的二溴化物合成了吡啶鎓）-5-（3 / 4-氨基甲酰基吡啶鎓）戊烷，并通过光谱数据对其进行了表征。研究了它们重新激活焦磷酸四乙酯抑制的小鼠总脑胆碱酯酶的能力，并将其与2-吡啶醛肟肟（2-PAM）进行了比较。与常规肟2-PAM相比，发现所有化合物都是更有效的乙酰胆碱酯酶活化剂，除了在第四位具有戊烯桥和氨基甲酰基的化合物（5a）。
• Synthesis and in-vitro reactivation screening of imidazolium aldoximes as reactivators of sarin and VX-inhibited human acetylcholinesterase (hAChE)
  作者：Rahul Sharma、Bhanushree Gupta、Arvind Kumar Sahu、Jyotiranjan Acharya、Manmohan L. Satnami、Kallol K. Ghosh

  DOI：10.1016/j.cbi.2016.04.034

  日期：2016.11

  and VX-inhibited human acetylcholinesterase (hAChE). The observed results were compared with the reactivation efficacy of standard reactivators; 2-PAM, obidoxime and HI-6. Amongst the synthesized oximes, 5a, 9a and 9b were found to be most potent reactivators against sarin-inhibited hAChE while in case of VX only 9a exhibited comparable reactivity with 2-PAM. Incorporation of pyridinium ring to the imidazole

  有机磷酸盐（OP）中毒的后处理涉及使用肟活化剂作为解毒剂。广泛研究了结构不同的肟，以检查它们对OP抑制的胆碱酯酶的动力学和机理行为。合成了一系列结构上相关的1,3-二取代-2-[（羟基亚氨基甲基）烷基]咪唑鎓卤化物（5a-5e，9a-9c），并进一步评估了它们的体外再活化能力以重新活化被沙林和VX抑制的物质。人乙酰胆碱酯酶（h AChE）。将观察到的结果与标准活化剂的活化效率进行了比较。2-PAM，obidoxime和HI-6。在合成的肟中，5a，9a和9b在VX的情况下，仅9a表现出与2-PAM相当的反应性，而被发现是对抗沙林抑制的h AChE的最有效的活化剂。吡啶鎓环与咪唑环的结合导致所制备的活化剂的活化强度大大提高。合成的活化剂的理化性质也得到了评估。
• Quaternary Salts of 3,3’-Bis-Pyridinium Monooximes Synthesis and Biological Activity
  作者：Arun K. Sikder、Ashim K. Ghosh、Devendra K. Jaiswal

  DOI：10.1002/jps.2600820308

  日期：1993.3

  Two new series of asymetrically substituted 3,3'-bis-pyridinium monooximes bridged by oxopropane and propane groups were synthesized and characterized by spectral data and acid dissociation constants (pKas). Both the in vitro reactivation potency, in experiments with lyophilized electric eel acetylcholinesterase (AChE) inhibited by diisopropylfluorophosphate, and in vivo protection efficacy against

  合成了由氧丙烷和丙烷基桥联的两个新系列的不对称取代的3,3'-双吡啶一肟，并通过光谱数据和酸解离常数（pKas）对其进行了表征。在用二异丙基氟磷酸盐抑制的冻干鳗鱼乙酰胆碱酯酶（AChE）的实验中，对体外再活化能力以及这些化合物在小鼠中对二异丙基氟磷酸盐中毒的体内保护作用进行了评估，并将其与曲美肟和2-吡啶-醛肟肟二甲硫醚进行了比较。还评估了化合物对AChE的体外抑制作用。与相应的丙烷衍生物相比，具有氧丙烷连接的化合物是更强的抑制剂和更弱的活化剂。在pKa，肟对AChE的抑制作用，抑制的乙酰胆碱酯酶的再活化和保护指数。与三甲肟和2-吡啶-醛肟甲硫代比相比，改变吡啶环上的取代基或改变吡啶环之间的连接基团不会提高解毒效果。
• Targeted Synthesis of 1-(4-Hydroxyiminomethylpyridinium)-3-pyridiniumpropane Dibromide – A New Nerve Agent Reactivator
  作者：Kamil Kuca、Kamil Musilek、Martin Paar、Daniel Jun、Petr Stodulka、Martina Hrabinova、Jan Marek

  DOI：10.3390/12081964

  日期：——

  Preparation of 1-(4-hydroxy-iminomethylpyridinium)-3-pyridiniumpropane dibromide is described. This compound represents a new acetylcholinesterase (AChE) reactivator, which has no substituents on the second pyridinium ring as found in other commonly used AChE reactivators. The reactivation ability of this reactivator was tested on tabun- and cyclosarin-inhibited AChE. According to the results obtained, the new compound (without substitution and with decreased molecule size) showed increased reactivation potency in case of cyclosarin inhibited AChE. A potent oxime for treatment of tabun and cyclosarin-caused intoxications was thus obtained via slight modification of the reactivator structure (compared to trimedoxime and K027).

  本文介绍了 1-(4-羟基-亚氨甲基吡啶鎓)-3-吡啶鎓丙烷二溴化物的制备方法。该化合物是一种新型乙酰胆碱酯酶（AChE）再活化剂，其第二个吡啶环上没有其他常用 AChE 再活化剂中的取代基。我们对塔崩和环沙林抑制的 AChE 的再激活能力进行了测试。结果表明，在环沙林抑制 AChE 的情况下，新化合物（未被取代且分子尺寸减小）显示出更强的再活化效力。因此，与曲美肟和 K027 相比，通过对反应活化剂结构的轻微修改，我们获得了一种用于治疗塔崩和环沙林引起的中毒的强效肟类化合物。
• Reactivation of Paraoxon-inhibited Acetylcholinesterase by Monoquaternary Pyridinium Oximes with<i>N</i>-Alkylbromide Side Chains
  作者：Hyun Myung Lee、Jin Soo Shin、Soo Bong Han、Yu Kyoung Jung、Meeheyin Kim、Sang-Ho Lee、Gyeunghaeng Hur、Young-Sik Jung

  DOI：10.1002/bkcs.10625

  日期：2016.1

  inhibition of acetylcholinesterase (AChE) in the human body. Various oxime reactivators were found to reactivate the inhibited AChE. Pralidoxime (2‐PAM) is one such representative oxime antidotes. However, its reactivation ability, as well as its action on the inhibited AChE of the central nervous system, is not sufficient, and therefore the discovery of new oxime reactivators is required. Here, oximes with

  有机磷神经毒剂通过抑制人体中的乙酰胆碱酯酶（AChE）引起神经毒性。发现各种肟再活化剂能再活化抑制的AChE。Pralidoxime（2-PAM）就是这样一种典型的肟解毒剂。但是，其再活化能力以及对中枢神经系统抑制的AChE的作用还不够，因此需要发现新的肟再活化剂。在这里，合成了具有N-溴代烷基的肟，并评估了它们被对氧磷抑制的对AChE的重新活化能力。