dimethyl 2-{[2-acetyl-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-2H-1,2-oxazin-3-yl]methyl}malonate | 1619976-58-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: dimethyl 2-{[2-acetyl-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-2H-1,2-oxazin-3-yl]methyl}malonate
• 英文别名: dimethyl 2-[[2-acetyl-4-(4-methoxyphenyl)-6,6-dimethyl-5H-oxazin-3-yl]methyl]propanedioate
• CAS: 1619976-58-7
• 化学式: C₂₁H₂₇NO₇
• 分子量: 405.448
• InChiKey: SFSFTLQXRNDQMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dimethyl 2-{[2-acetyl-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-2H-1,2-oxazin-3-yl]methyl}malonate 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 40.0~50.0 ℃ 、4.0 MPa 条件下， 反应 4.0h， 以96%的产率得到dimethyl rel-2-{[(3S*,4R*)-2-acetyl-4-(4-methoxyphenyl)-6,6-dimethyl-1,2-oxazinan-3-yl]methyl}malonate
  参考文献：
  名称：

  酰化条件下N-氧化物的串联脱氧/卤化作用：范围和原位红外光谱研究

  摘要：

  1,2-恶嗪N-氧化物与酰基溴的不寻常酰化反应会通过形成分子溴作为中间体来生成3-溴甲基-取代的2 H - 1,2-恶嗪。所开发的方法已成功地用于药物相关分子的立体选择性合成中。

  DOI：

  10.1002/ejoc.201900131
• 作为产物：
  描述：

  4-(4-methoxyphenyl)-3,6,6-trimethyl-5,6-dihydro-4H-1,2-oxazine 2-oxide 在 乙酰溴 、 三甲基溴硅烷 、 potassium tert-butylate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 dimethyl 2-{[2-acetyl-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-2H-1,2-oxazin-3-yl]methyl}malonate
  参考文献：
  名称：

  Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase

  摘要：

  Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethy1-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 mu M, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of -1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (logP = 2.66), suggesting a potential ability to penetrate the blood-brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer's agents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.040

文献信息

• Tandem Deoxygenation/Halogenation of <i>N</i> -Oxides Under Acylation Conditions: Scope and In Situ IR Spectroscopic Study
  作者：Roman S. Malykhin、Ivan S. Golovanov、Sema L. Ioffe、Alexey Yu. Sukhorukov

  DOI：10.1002/ejoc.201900131

  日期：2019.7.14

  Unusual acylation of 1,2‐oxazine N‐oxides with acyl bromides produces 3‐bromomethyl‐substituted 2H‐1,2‐oxazines via the formation of molecular bromine as intermediate. The developed process was successfully exploited in the stereoselective synthesis of pharmaceutically relevant molecules.

  1,2-恶嗪N-氧化物与酰基溴的不寻常酰化反应会通过形成分子溴作为中间体来生成3-溴甲基-取代的2 H - 1,2-恶嗪。所开发的方法已成功地用于药物相关分子的立体选择性合成中。
• Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase
  作者：Alexey Yu. Sukhorukov、Anilkumar C. Nirvanappa、Jagadish Swamy、Sema L. Ioffe、Shivananju Nanjunda Swamy、Basappa、Kanchugarakoppal S. Rangappa

  DOI：10.1016/j.bmcl.2014.05.040

  日期：2014.8

  Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethy1-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 mu M, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of -1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (logP = 2.66), suggesting a potential ability to penetrate the blood-brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer's agents. (C) 2014 Elsevier Ltd. All rights reserved.