3-(bromomethyl)-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine | 910916-54-0

• 英文名称: 3-(bromomethyl)-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine
• 英文别名: 3-(Bromomethyl)-4-(4-methoxyphenyl)-6,6-dimethyl-4,5-dihydrooxazine
• CAS: 910916-54-0
• 化学式: C₁₄H₁₈BrNO₂
• 分子量: 312.206
• InChiKey: XHGITPXOVHIWRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(bromomethyl)-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine 在 potassium tert-butylate 、 sodium cyanoborohydride 作用下， 以 溶剂黄146 为溶剂， 反应 0.33h， 生成 dimethyl 2-[[(3S,4S)-4-(4-methoxyphenyl)-6,6-dimethyloxazinan-3-yl]methyl]propanedioate
  参考文献：
  名称：

  The first synthesis and molecular docking studies of diastereomerically pure substituted 4-amino-7-hydroxyheptanoic acids

  摘要：

  Diastereoselective synthesis of 4-amino-7-hydroxyheptanoic acids 1, new GABA analogues, was performed involving reduction of C-3 functionalized 5,6-dihydro-4H-1,2-oxazines available from nitroethane. Molecular docking studies showed that amino acids of type 1 may bind to GABA transaminase, however, no inhibition was observed in the experiments with the enzyme.

  DOI：

  10.1016/j.mencom.2011.07.002
• 作为产物：
  描述：

  1-methoxy-4-((E)-2-nitroprop-1-enyl)benzene 在 三甲基溴硅烷 、 四氯化锡 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 3-(bromomethyl)-4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine
  参考文献：
  名称：

  从硝基乙烷合成 3-取代的 5,6-二氢-4H-1,2-恶嗪的简便方法

  摘要：

  描述了一种从硝基乙烷合成 C-3-官能化 5,6-二氢-4H-1,2-恶嗪的新型高效四步法。包括制备3-甲基取代的六元环状硝酸酯、3-(溴甲基)-取代的5,6-二氢-4H-1,2-恶嗪中间体、溴的亲核取代。来自硝基乙烷的目标 C-3-官能化恶嗪的总产率为 15-30%。

  DOI：

  10.1055/s-2006-958930

文献信息

• A General Metal-Assisted Synthesis of α-Halo Oxime Ethers from Nitronates and Nitro Compounds
  作者：Alexey Yu. Sukhorukov、Maria A. Kapatsyna、Tammy Lim Ting Yi、Hyeong Ryool Park、Yana A. Naumovich、Petr A. Zhmurov、Yulia A. Khomutova、Sema L. Ioffe、Vladimir A. Tartakovsky

  DOI：10.1002/ejoc.201403083

  日期：2014.12

  α-halo oxime ethers from readily accessible nitronates and nitro compounds via bis(oxy)enamines is reported. A key step of the strategy involves the unprecedented reaction of bis(oxy)enamines with a metal (Co, Zn, Mg, Mn) halide that acts as both a promoter and halide (Br, I, Cl) source. A variety of cyclic and acyclic ethers of α-halo oximes, including previously unavailable trimethylsilyl ethers of α-iodo

  报道了一种通过双（氧）烯胺从容易获得的硝基化合物和硝基化合物合成 α-卤代肟醚的方法。该策略的一个关键步骤涉及双（氧）烯胺与金属（Co、Zn、Mg、Mn）卤化物的前所未有的反应，该卤化物既作为促进剂又作为卤化物（Br、I、Cl）源。各种 α-卤代肟的环状和非环状醚，包括以前无法获得的 α-碘肟的三甲基甲硅烷基醚，已经以良好到高的产率合成。
• A Convenient Procedure for the Synthesis of <i>N</i>-Acetyl-5,6-dihydro-2<i>H</i>-1,2-oxazines
  作者：Alexey Lesiv、Sema Ioffe、Pavel Ivashkin、Alexey Sukhorukov、Oleg Eliseev、Yulja Khomutova

  DOI：10.1055/s-2007-990857

  日期：2007.11

  Acetylation of 5,6-dihydro-4H-1,2-oxazines with an acetyl bromide/acetic anhydride mixture provides a general and quite simple procedure for the synthesis of N-acetyl-5,6-dihydro-2H-1,2-oxazines.

  乙酰溴/乙酸酐混合物对5,6-二氢-4H-1,2-噁嗪进行乙酰化反应，提供了一种通用且颇为简单的N-乙酰-5,6-二氢-2H-1,2-噁嗪合成方法。
• Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells
  作者：Chaithanya Somu、Chakrabhavi Dhananjaya Mohan、Sachin Ambekar、Dukanya、Shobith Rangappa、CP Baburajeev、Alexey Sukhorukov、Srishti Mishra、Muthu K Shanmugam、Arunachalam Chinnathambi、Tahani Awad Alahmadi、Sulaiman Ali Alharbi、Basappa、Kanchugarakoppal S. Rangappa

  DOI：10.1016/j.btre.2020.e00438

  日期：2020.3

  Constitutive activation of NF-κB is associated with proinflammatory diseases and suppression of the NF-κB signaling pathway has been considered as an effective therapeutic strategy in the treatment of various cancers including hepatocellular carcinoma (HCC). Herein, we report the synthesis of 1,2 oxazines and their anticancer potential. The antiproliferative studies presented 3-((4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)methyl)-4-phenyl-4,4a,5,6,7,7a-hexahydrocyclopenta [e][1,2]oxazine(3i) as a lead cytotoxic agent against HCC cells. Flow cytometric analysis showed that 3i caused a substantial increase in the subG1 cell population. Annexin-V-FITC-PI staining showed a significant increase in the percentage of apoptotic cells on treatment with 3i. Transfection with p65 siRNA significantly reduced the 3i induced DNA fragmentation indicating that 3i may primarily mediate its proapoptotic effects by abrogating the NF-κB signaling. In addition, treatment of HCC cells with 3i decreased the DNA binding ability of NF-κB and NF-κB-dependent luciferase expression. Taken together, this report introduces 1,2-oxazine that potently targets the NF-κB signaling pathway in HCC cells.
• 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.