2-<(hydroxyimino)methyl>-1-<(chloromethoxy)methyl>pyridinium chloride | 27123-11-1

• 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: 2-<(hydroxyimino)methyl>-1-<(chloromethoxy)methyl>pyridinium chloride
• 英文别名: 1-((chloromethoxy)methyl)-2-((hydroxyimino)methyl)pyridinium chloride；1-[(Chloromethoxy)methyl]-2-formyl-pyridinium Chloride Oxime；N-[[1-(chloromethoxymethyl)pyridin-1-ium-2-yl]methylidene]hydroxylamine;chloride
• CAS: 27123-11-1
• 化学式: C₈H₁₀ClN₂O₂*Cl
• 分子量: 237.086
• InChiKey: DZKHTMVXEHCDMQ-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于二甲基亚砜、甲醇、水

计算性质

• 辛醇/水分配系数(LogP)：
  -2.04
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  45.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-<(hydroxyimino)methyl>-1-<(chloromethoxy)methyl>pyridinium chloride 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以42%的产率得到1-((azidomethoxy)methyl)-2-((hydroxyimino)methyl)pyridinium chloride
  参考文献：
  名称：

  由三唑-肟化合物库（乙酰胆碱酯酶的活化剂）逆转禁忌毒素的毒性

  摘要：

  乙酰胆碱酯酶（AChE）是一种降解神经递质乙酰胆碱的酶，当被有机磷化合物（OPs）（例如神经毒剂和杀虫剂）共价抑制时，可以被肟重新激活。然而，由于标准吡啶鎓醛肟肟解毒剂的低活化作用，塔邦仍然是最危险的神经制剂之一。因此，寻找最佳的活化剂来预防塔宾毒性和进行暴露后治疗仍然是一个挑战。在这项研究中，我们分析了炔烃和叠氮化物结构单元之间主要通过CuAAC三唑连接而合成的111种新型亲核肟的活化潜能。我们鉴定了几种肟，它们在禁忌暴露的人AChE中具有显着提高的体外再激活潜力，并且在禁忌暴露的小鼠中具有体内解毒作用。

  DOI：

  10.1002/chem.201805051
• 作为产物：
  描述：

  二氯甲基醚 、 吡啶-2-甲醛肟氯甲烷盐 以 氯仿 为溶剂， 反应 4.0h， 以78.7%的产率得到2-<(hydroxyimino)methyl>-1-<(chloromethoxy)methyl>pyridinium chloride
  参考文献：
  名称：

  Process for halomethyl ethers of hydroxyiminomethyl quaternary pyridinium salts

  摘要：

  一种1-(羟基亚胺甲基-1-吡啶基)-3-(卤代甲基)-2-氧丙烷的卤化物盐是通过将吡啶醛肟加入双(卤代甲基)醚中以使双(卤代甲基)醚在加入过程中始终保持过量来制备的。这个过程以高收率和纯度产生了1-(羟基亚胺甲基-1-吡啶基)-3-(卤代甲基)-2-氧丙烷的卤化物盐，这便于其作为中间体用于制造不对称取代的1,3-二(1-吡啶基)-2-氧丙烷，这类化合物通常用作对各种有毒物质的通用解毒剂。这类化合物的一个突出成员是1-(2-羟基亚胺甲基-1-吡啶基)-3-(4-碳酰胺基-1-吡啶基)-2-氧丙烷的二甲磺酸盐。在制造这些化合物的最后纯化步骤中，推荐使用巯基烷基功能化的聚合物作为首选的金属离子清除剂。

  公开号：

  US20060183777A1

文献信息

• Reactivation potency of fluorinated pyridinium oximes for acetylcholinesterases inhibited by paraoxon organophosphorus agent
  作者：Hee Chun Jeong、Nam Sook Kang、No-Joong Park、Eul Kyun Yum、Young-Sik Jung

  DOI：10.1016/j.bmcl.2008.12.070

  日期：2009.2

  purpose of developing new oxime reactivators of acetylcholinesterases (AChE) that have been inhibited by organophosphorus agents, emphasis was given to the finding that the lipophilic nature of fluorinated compounds is responsible for their enhanced transport across the blood brain barrier (BBB). As a result, we have designed and synthesized the fluorinated oxime derivatives, which quantum mechanical

  为了开发已被有机磷试剂抑制的乙酰胆碱酯酶（AChE）的新肟活化剂，重点是发现氟化化合物的亲脂性是其跨血脑屏障（BBB）转运增强的原因。结果，我们设计并合成了氟化肟衍生物，其量子力学计算表明，它们应比非氟化类似物具有更大的亲脂性和BBB渗透性。在这项研究中探索的化合物中，发现有4种具有对氧磷抑制的家蝇（HF）AChE的再激活能力最高。
• Bis-quaternary pyridinium-2-aldoxime salts and a process for their
  申请人：Merck Patent Gesellschaft mit beschrankter Haftung

  公开号：US04128651A1

  公开（公告）日：1978-12-05

  Bis-quaternary pyridinium-2-aldoxime salts of the formula ##STR1## wherein R is --CO--R.sup.1, --CO--NR.sup.2 R.sup.3 or --COOR.sup.4 ; R.sup.1 is alkyl of 1 - 6 carbon atoms, cyclohexyl, Ar or benzyl; R.sup.2 is H, alkyl of 1 - 6 carbon atoms, cyclohexyl, Ar, aralkyl of 7 - 13 carbon atoms or 2-pyrimidyl; R.sup.3 is alkyl of 2 - 6 carbon atoms, cyclohexyl, Ar, aralkyl of 7 - 13 carbon atoms or 2-pyrimidyl; R.sup.4 is alkyl of 2 - 6 carbon atoms, cyclohexyl, Ar or benzyl; Ar is phenyl or phenyl monosubstituted or polysubstituted by alkyl of 1 - 4 carbon atoms, methoxy, Cl, or naphthyl and X is Cl, Br or I, are antidotes for phosphorus-containing pesticides and chemical warfare agents.

  公式为##STR1##的双季铵吡啶-2-醛肟盐，其中R为--CO--R.sup.1，--CO--NR.sup.2 R.sup.3或--COOR.sup.4; R.sup.1为1-6个碳原子的烷基，环己烷基，Ar或苄基; R.sup.2为H，1-6个碳原子的烷基，环己烷基，Ar，7-13个碳原子的芳基烷基或2-嘧啶基; R.sup.3为2-6个碳原子的烷基，环己烷基，Ar，7-13个碳原子的芳基烷基或2-嘧啶基; R.sup.4为2-6个碳原子的烷基，环己烷基，Ar或苄基; Ar为苯基或被1-4个碳原子的烷基，甲氧基，Cl或萘基单取代或多取代，X为Cl，Br或I，是含磷农药和化学战剂的解毒剂。
• Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 2. Preparation and in vitro and in vivo evaluaton of 1-(alkoxymethyl)-2-[(hydroxyimino)methyl]-3-methylimidazolium halides for reactivation of organophosphorus-inhibited acetylcholinesterases
  作者：Clifford D. Bedford、Ralph N. Harris、Robert A. Howd、Dane A. Goff、Gary A. Koolpe、M. Petesch、Alexi Miller、Harold W. Nolen、H. A. Musallam

  DOI：10.1021/jm00122a034

  日期：1989.2

  A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-2-butyl methyl-phosphonofluoridate (soman, GD). All new compounds were characterized for (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol-buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivation of EPMP-inhibited AChEs. For GD-inhibited AChEs, maximal reactivation was used to compare compounds since rapid phosphonyl enzyme dealkylation "aging" complicated interpretation of kinetic constants. For comparison, we also evaluated three known pyridinium therapeutics, 2-PAM, HI-6, and toxogonin. In vivo evaluation in mice revealed that when selected imidazolium compounds were coadministered with atropine sulfate, they were effective in providing lifesaving protection against both GD and EPMP challenges. This was a major accomplishment in the search for effective anticholinesterase therapeutics--the synthesis and preliminary evaluation of the first new monoquaternary soman antidotes with potencies superior to 2-PAM. Significantly, there was an apparent inverse relationship between in vitro and in vivo results; the most potent in vivo compounds proved to be the poorest in vitro reactivators. These results suggested that an alternative and possibly novel antidotal mechanism of protective action may be applicable for the imidazolium aldoximes. Selected compounds were also evaluated for their inhibition of AChE phosphorylation by GD and antimuscarinic and antinicotinic receptor blocking effects.
• US4128651A
  申请人：——

  公开号：US4128651A

  公开（公告）日：1978-12-05