(E)-4-(methyl)picolinaldehyde oxime | 57093-20-6

• 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: (E)-4-(methyl)picolinaldehyde oxime
• 英文别名: (E)-4-methylpicolinaldehyde oxime；(E)-2-Hydroxyiminomethyl-4-methyl-pyridin；(NE)-N-[(4-methylpyridin-2-yl)methylidene]hydroxylamine
• CAS: 57093-20-6
• 化学式: C₇H₈N₂O
• 分子量: 136.153
• InChiKey: LMZNISSHAGPBLK-WEVVVXLNSA-N

物化性质

• 熔点：
  171-173 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  266.3±28.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4-(methyl)picolinaldehyde oxime 、 碘甲烷 以 丙酮 为溶剂， 反应 20.0h， 以72%的产率得到(E)-2-((hydroxyimino)methyl)-1,4-dimethylpyridin-1-ium iodide
  参考文献：
  名称：

  Methyl Scanning and Revised Binding Mode of 2-Pralidoxime, an Antidote for Nerve Agent Poisoning

  摘要：

  Organophosphorus nerve agents (OPNAs) inhibit acetylcholinesterase (AChE) and, despite the Chemical Weapons Convention arms control treaty, continue to represent a threat to both military personnel and civilians. 2-Pralidoxime (2-PAM) is currently the only therapeutic countermeasure approved by the United States Food and Drug Administration for treating OPNA poisoning. However, 2-PAM is not centrally active due to its hydrophilicity and resulting poor blood-brain barrier permeability; hence, these deficiencies warrant the development of more hydrophobic analogs. Specifically, gaps exist in previously published structure activity relationship (SAR) studies for 2-PAM, thereby making it difficult to rationally design novel analogs that are concomitantly more permeable and more efficacious. In this study, we methodically performed a methyl scan on the core pyridinium of 2-PAM to identify ring positions that could tolerate both additional steric bulk and hydrophobicity. Subsequently, SAR-guided molecular docking was used to rationalize hydropathically feasible binding modes for 2-PAM and the reported derivatives. Overall, the data presented herein provide new insights that may facilitate the rational design of more efficacious 2-PAM analogs.

  DOI：

  10.1021/acsmedchemlett.9b00586
• 作为产物：
  描述：

  (4-甲基-吡啶-2-基)-甲醇 在 manganese(IV) oxide 、 盐酸羟胺 、 potassium carbonate 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 17.0h， 生成 (E)-4-(methyl)picolinaldehyde oxime
  参考文献：
  名称：

  [EN] ANALOGS OF 2-PRALIDOXIME AS ANTIDOTES AGAINST ORGANOPHOSPHORUS NERVE AGENTS
  [FR] ANALOGUES DE 2-PRALIDOXIME EN TANT QU'ANTIDOTES CONTRE DES AGENTS NEUROTOXIQUES ORGANOPHOSPHORÉS

  摘要：

  公开号：

  WO2020027905A3

文献信息

• ARENA F.; MANNA F.; PIZZA C.; STEIN M. L.; GRIFANTINI M., J. MED. CHEM. <JMCM-AR>, 1975, 18, NO 11, 1147-1150
  作者：ARENA F.、 MANNA F.、 PIZZA C.、 STEIN M. L.、 GRIFANTINI M.

  DOI：——

  日期：——
• Analogs of 2-Pralidoxime as Antidotes Against Organophosphorus Nerve Agents
  申请人：University of Pittsburgh - Of the Commonwealth System of Higher Education

  公开号：US20210317084A1

  公开（公告）日：2021-10-14

  Provided herein are compounds useful in treating exposure to an organophosphorus compound, such as a nerve agent, pesticide, or, generally, an acetylcholinesterase inhibitor, such as sarin. Compositions, e.g. pharmaceutical compositions or dosage forms, comprising the compounds also are provided herein. Methods of treating a patient exposed to a nerve agent, pesticide, or, generally, an acetylcholinesterase inhibitor, e.g., an organophosphorus compound, such as sarin, also are provided.