N-(3-azido-1-phenylpropyl)-2-hydroxyiminoacetamide | 1620488-63-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-azido-1-phenylpropyl)-2-hydroxyiminoacetamide
• CAS: 1620488-63-2
• 化学式: C₁₁H₁₃N₅O₂
• 分子量: 247.257
• InChiKey: HNVSUUSQYNKMTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.0
• 重原子数：
  18.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  110.45
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(3-azido-1-phenylpropyl)-2-hydroxyiminoacetamide 、 2-甲基-1-(2-丙炔-1-基)-1H-咪唑 在 铜 作用下， 生成 2-hydroxy-imino-N-(3-(4-((2-methyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylpropyl)acetamide
  参考文献：
  名称：

  Design and synthesis of N-substituted-2-hydroxyiminoacetamides and interactions with cholinesterases

  摘要：

  Within this study, we designed and synthesized four new oxime compounds of the N-substituted 2-hydroxyiminoacetamide structure and evaluated their interactions with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Our aim was to explore the possibility of extending the dual-binding mode of interaction between the enzyme and the inhibitor to a so-called triple-binding mode of interaction through the introduction of an additional binding moiety. N-substituted 2-hydroxyiminoacetamide 1 was prepared via BOP catalyzed amidation of hydroxyiminoacetic acid with 3-azido-1-phenylpropylamine. An azide group enabled us to prepare more elaborate structures 2-4 by the copper-catalyzed azide-alkyne cycloaddition. The new compounds 1-4 differed in their presumed AChE peripheral site binding moiety, which ranged from an azide group to functionalized heterocycles. Molecular docking studies revealed that all three binding moieties are involved in the non-covalent interactions with ChEs for all of the four compounds, albeit not always in the complete accordance with the proposed hypothesis. All of the four compounds reversibly inhibited the ChEs with their inhibition potency increasing in the same order for both enzymes (1 < 2 < 4 < 3). A higher preference for binding to BChE (K-I from 0.30 mu mol/L to 130 mu mol/L) over AChE (K-I from 50 mmol/L to 1200 mmol/L) was observed for all of the compounds. Compounds were screened for reactivation of cyclosarin-, sarin-and VX-inhibited AChE and BChE. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.cbi.2016.05.035
• 作为产物：
  描述：

  1-苯基-2-丙烯基胺 在 Candida antarctica lipase B 、 叠氮磷酸二苯酯 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 9-硼双环[3.3.1]壬烷 、 三氟乙酸 、 zinc dibromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 异丙醚 、 甲苯 为溶剂， 反应 8.0h， 生成 N-(3-azido-1-phenylpropyl)-2-hydroxyiminoacetamide
  参考文献：
  名称：

  Enzyme-catalyzed cascade synthesis of hydroxyiminoacetamides

  摘要：

  In order to synthesize N-(3-azido-1-phenylpropyl)-2-hydroxyiminoacetamide, a key compound for the preparation of acetylcholinesterase (AChE) reactivators of the N-substituted 2-hydroxyiminoacetamide type, it was necessary to develop a method for forming an amide bond between an ethyl glyoxylate oxime and an amine. Using Candida antarctica lipase B (CAL-B) in a cascade enzyme-BOP catalyzed reaction, the efficient synthesis of the target hydroxyiminoacetamide was achieved. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.06.027

文献信息

• Enantioseparation, <i>in vitro</i> testing, and structural characterization of triple-binding reactivators of organophosphate-inhibited cholinesterases
  作者：Nikola Maraković、Anamarija Knežević、Igor Rončević、Xavier Brazzolotto、Zrinka Kovarik、Goran Šinko

  DOI：10.1042/bcj20200192

  日期：2020.8.14

  determined for the complex of oxime III within human BChE, confirming that all three binding groups interacted with active site residues. In the case of BChE inhibited by GF, oximes I (kr = 207 M-1 min-1) and III (kr = 213 M-1 min-1) showed better reactivation efficiency than the reference oxime 2-PAM. Finally, the key mechanistic steps in the reactivation of GF-inhibited BChE with oxime III were modeled using

  分离由外消旋2-羟基亚氨基-N-（叠氮苯丙基）乙酰胺衍生的三结合肟活化剂的对映异构体，并测试抑制和再活化被塔邦（GA），环沙蛋白（GF）抑制的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE） ），沙林（GB）和VX。两种酶对2-羟基亚氨基-N-（叠氮苯基丙基）乙酰胺（I）的甲基咪唑衍生物（III）显示出最大的亲和力。确定了人BChE中肟III的配合物的晶体结构，证实了所有三个结合基团均与活性位点残基相互作用。在GF抑制BChE的情况下，肟I（kr = 207 M-1 min-1）和III（kr = 213 M-1 min-1）比参考肟2-PAM表现出更好的再活化效率。最后，