Pyridoxaloxime | 708-08-7

• 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: Pyridoxaloxime
• 英文别名: 3-hydroxy-5-hydroxymethyl-2-methylpyridine-4-carbaldehyde oxime；pyridoxal oxime；2-Methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine oxime；4-(hydroxyiminomethyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol
• CAS: 708-08-7
• 化学式: C₈H₁₀N₂O₃
• 分子量: 182.179
• InChiKey: QXKIIRAOFHLZMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  85.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Pyridoxaloxime 在 N,N-二异丙基乙胺 、 对甲苯磺酰氯 作用下， 以 乙腈 为溶剂， 生成 (7-methyl-oxazolo[5,4-c]pyridin-4-yl)-methanol
  参考文献：
  名称：

  羟基肟作为有机磷神经活性剂传感器

  摘要：

  查找并销毁：构造了一系列肟以同时检测和解毒基于有机磷的神经毒剂。它们起光学传感器的作用，利用肟的反应性并结合一个β-羟基，从肟-有机磷的中间物种进行分子内环化。产生的异恶唑产生增强的荧光信号，该信号报告神经药的存在和破坏。

  DOI：

  10.1002/anie.200902820
• 作为产物：
  描述：

  吡哆醛盐酸盐 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 以57 %的产率得到Pyridoxaloxime
  参考文献：
  名称：

  定制的吡哆醛探针揭示了关键细菌病原体中新的辅因子依赖性靶标和抗生素命中

  摘要：

  对抗细菌大流行需要前所未有的目标。应用了一套吡哆醛探针，这些探针渗透到关键病原体的细胞代谢中，并结合到磷酸吡哆醛依赖性酶中。化学蛋白质组学促进了以前未知成员的功能表征和抗生素命中分子的基本目标的鉴定。

  DOI：

  10.1002/anie.202117724

文献信息

• An Efficient Synthesis of Pyridoxal Oxime Derivatives under Microwave Irradiation
  作者：Dajana Gašo-Sokač、Valentina Bušić、Mario Cetina、Marijana Jukić

  DOI：10.3390/molecules19067610

  日期：——

  Quaternary salts of pyridoxal oxime have been synthesized by the quaternization of pyridoxal oxime with substituted phenacyl bromides using microwave heating. Microwave-assisted rapid synthesis was done both in solvent (acetone) and under solvent-free conditions. Good to excellent yields (58%-94%) were obtained in acetone in very short reaction times (3-5 min) as well as in the solvent-free procedure

  吡哆醛肟的季盐已通过使用微波加热将吡哆醛肟与取代的苯甲酰溴季铵化而合成。微波辅助快速合成在溶剂（丙酮）和无溶剂条件下进行。在丙酮中在非常短的反应时间（3-5 分钟）以及在无溶剂程序中（42%-78%）在非常短的反应时间（7- 10 分钟）。介绍了制备吡哆醛肟季盐的有效方法，具有环保、易于处理和反应时间较短的优点。通过单晶 X 射线衍射法明确证实了化合物 7 的结构，其中 4-氟苯酰基部分与吡啶环氮原子键合。
• Microwave-assisted Quaternization of Various Pyridine Derivatives and their Antibacterial Activity
  作者：Valentina Bušić、Hrvoje Pavlović、Sunčica Roca、Dražen Vikić-Topić、Dajana Gašo-Sokač

  DOI：10.5562/cca2937

  日期：——

  ne, 2-amino-4-chloromethylthiazole hydrochloride, methyl iodide, 1, 3-diiodopropane and 1, 3-dibromopropane are reported. The synthesis yield by microwave dielectric heating is improved and reaction time shortened compared to conventional heating. Some of the synthesized compounds were tested regarding their potential antibacterial activity against two Gram-positive and two Gram-negative bacteria.

  已经研究了许多吡啶鎓衍生物的生物学和药理活性。它们的重要性在于其有效的抗微生物，抗病毒，抗高血压和免疫刺激活性。一些吡啶鎓醛肟衍生物是针对有机磷酸酯中毒的潜在解毒剂。在这项研究中，吡啶，α-甲基吡啶，吡啶-4-醛肟，吡啶-2-醛肟，烟酰胺，异烟酰胺和吡ot肟的微波加热下季铵化反应与不同的亲电试剂：2-溴-4'-硝基苯乙酮，2-据报道有氨基-4-氯甲基噻唑盐酸盐，甲基碘，1，3-二碘丙烷和1，3-二溴丙烷。与常规加热相比，微波介电加热可提高合成产率，并缩短反应时间。测试了一些合成的化合物对两种革兰氏阳性和两种革兰氏阴性细菌的潜在抗菌活性。抗菌评估显示1- [2-（4-硝基苯基）-2-氧代乙基]溴化吡啶鎓对G阳性和G阴性细菌的疗效相对较高。
• Hydroxy Oximes as Organophosphorus Nerve Agent Sensors
  作者：Trevor J. Dale、Julius Rebek

  DOI：10.1002/anie.200902820

  日期：2009.10.5

  Find and destroy: A series of oximes were constructed to simultaneously detect and detoxify organophosphorus‐based nerve agents. They function as optical sensors employing the oxime reactivity and incorporating a β‐hydroxyl group to undergo an intramolecular cyclization from the intermediate oxime–organophosphorus species. The generated isoxazole produces an enhanced fluorescent signal that reports

  查找并销毁：构造了一系列肟以同时检测和解毒基于有机磷的神经毒剂。它们起光学传感器的作用，利用肟的反应性并结合一个β-羟基，从肟-有机磷的中间物种进行分子内环化。产生的异恶唑产生增强的荧光信号，该信号报告神经药的存在和破坏。
• Extensive Intramolecular and Intermolecular Interactions in Two Quaternary Salts of the Pyridoxal Oxime
  作者：Mario Cetina、Ante Nagl、Dajana Gašo-Sokač、Spomenka Kovač、Valentina Bušić、Dijana Saftić

  DOI：10.1007/s10870-012-0312-y

  日期：2012.7

  Two derivatives of pyridoxal oxime (1) were prepared by quaternization of pyridoxal oxime with phenacyl bromide and 2-methoxyphenacyl bromide. The crystal structures of the 1-phenacyl-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (2) and the novel 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(2′-methoxyphenacyl) pyridinium bromide (3) have been determined by

  吡哆醛肟的两种衍生物 (1) 通过吡哆醛肟与苯甲酰溴和 2-甲氧基苯甲酰溴的季铵化制备。1-phenacyl-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (2) 和新型 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-( 2'-甲氧基苯甲酰溴化吡啶鎓 (3) 已通过 X 射线衍射法测定。这两种吡哆醛肟苯甲酰基衍生物的构象被许多分子内氢键锁定。2和3中的O-H···Br、C-H···Br和C-H···O氢键形成复杂的三维网络。3的超分子结构还包含连接相邻阳离子的C-H···π和π···π相互作用。图形摘要在吡哆醛肟的两种衍生物中，
• Potential of Vitamin B6 Dioxime Analogues to Act as Cholinesterase Ligands
  作者：Dajana Gašo Sokač、Antonio Zandona、Sunčica Roca、Dražen Vikić-Topić、Gabriela Lihtar、Nikola Maraković、Valentina Bušić、Zrinka Kovarik、Maja Katalinić

  DOI：10.3390/ijms232113388

  日期：——

  Seven pyridoxal dioxime quaternary salts (1–7) were synthesized with the aim of studying their interactions with human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The synthesis was achieved by the quaternization of pyridoxal monooxime with substituted 2-bromoacetophenone oximes (phenacyl bromide oximes). All compounds, prepared in good yields (43–76%) and characterized by 1D and 2D NMR spectroscopy, were evaluated as reversible inhibitors of cholinesterase and/or reactivators of enzymes inhibited by toxic organophosphorus compounds. Their potency was compared with that of their monooxime analogues and medically approved oxime HI-6. The obtained pyridoxal dioximes were relatively weak inhibitors for both enzymes (Ki = 100–400 µM). The second oxime group in the structure did not improve the binding compared to the monooxime analogues. The same was observed for reactivation of VX-, tabun-, and paraoxon-inhibited AChE and BChE, where no significant efficiency burst was noted. In silico analysis and molecular docking studies connected the kinetic data to the structural features of the tested compound, showing that the low binding affinity and reactivation efficacy may be a consequence of a bulk structure hindering important reactive groups. The tested dioximes were non-toxic to human neuroblastoma cells (SH-SY5Y) and human embryonal kidney cells (HEK293).

  合成了七种吡哆醛二肟季铵盐（1-7），旨在研究它们与人类乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的相互作用。合成是通过将吡哆醛单肟与取代的2-溴乙酰苯肟（苯乙酰溴肟）季铵化而实现的。所有化合物均以良好的收率（43-76％）制备，并通过1D和2D NMR光谱表征，被评估为乙酰胆碱酯酶的可逆抑制剂和/或被有毒有机磷化合物抑制的酶的再活化剂。它们的效力与其单肟类似物和经医学批准的肟类HI-6进行了比较。所得的吡哆醛二肟对两种酶都是相对较弱的抑制剂（Ki = 100-400 µM）。结构中的第二个肟基与单肟类似物相比并没有改善结合。在重新激活被VX、塔本和对硫磷酸酯抑制的AChE和BChE方面也是如此，没有观察到显着的效率爆发。通过计算机模拟和分子对接研究，将动力学数据与测试化合物的结构特征联系起来，表明低结合亲和力和再活化效力可能是由于臃肿的结构阻碍了重要的反应基团。测试的二肟对人神经母细胞瘤细胞（SH-SY5Y）和人胚胎肾细胞（HEK293）无毒。