2-<(hydroxyimino)methyl>-1-<<<2-<(hydroxyimino)methyl>-3-methyl-1H-imidazolium-1-yl>methoxy>methyl>pyridinium dichloride | 93490-44-9

• 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-<<<2-<(hydroxyimino)methyl>-3-methyl-1H-imidazolium-1-yl>methoxy>methyl>pyridinium dichloride
• 英文别名: 2-[(hydroxyimino)methyl]-1-[({2-[(hydroxyimino)methyl]-3-methyl-1H-imidazolium-1-yl}methoxy)methyl]pyridinium dichloride；[1-[[3-methyl-2-(oxoazaniumylmethylidene)imidazol-1-yl]methoxymethyl]pyridin-2-ylidene]methyl-oxoazanium;chloride
• CAS: 93490-44-9
• 化学式: C₁₃H₁₇N₅O₃*2Cl
• 分子量: 362.216
• InChiKey: DUTDSQYAKJKBHP-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -3.15
• 重原子数：
  22.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  87.1
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  2-<(hydroxyimino)methyl>-1-<(chloromethoxy)methyl>pyridinium chloride 、 1-methyl-1H-imidazole-2-carbaldehyde oxime 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以11%的产率得到2-<(hydroxyimino)methyl>-1-<<<2-<(hydroxyimino)methyl>-3-methyl-1H-imidazolium-1-yl>methoxy>methyl>pyridinium dichloride
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00122a034