3-(bromomethyl)-4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine | 910916-64-2

• 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: 3-(bromomethyl)-4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine
• 英文别名: 3-(Bromomethyl)-4-(4-chlorophenyl)-6,6-dimethyl-4,5-dihydrooxazine
• CAS: 910916-64-2
• 化学式: C₁₃H₁₅BrClNO
• 分子量: 316.625
• InChiKey: YTXQNAFFGYUUEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(bromomethyl)-4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine 、 乙酰溴 在 乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以94%的产率得到2-acetyl-3-(bromomethyl)-4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-1,2-oxazine
  参考文献：
  名称：

  A Convenient Procedure for the Synthesis of N-Acetyl-5,6-dihydro-2H-1,2-oxazines

  摘要：

  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。

  DOI：

  10.1055/s-2007-990857
• 作为产物：
  描述：

  1-氯-4-[(1E)-2-硝基-1-丙烯-1-基]苯 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-chlorophenyl)-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。
• Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2
  作者：V. Srinivas、Chakrabhavi Dhananjaya Mohan、C.P. Baburajeev、Shobith Rangappa、Swamy Jagadish、Julian E. Fuchs、Alexey Yu. Sukhorukov、Chandra、Daniel J. Mason、Kothanahally Shivaramu Sharath Kumar、Mahendra Madegowda、Andreas Bender、Basappa、Kanchugarakoppal Subbegowda Rangappa

  DOI：10.1016/j.bmcl.2015.05.047

  日期：2015.8

  combustion synthesis-bismuth oxide (Bi2O3) as catalyst for the simple and efficient synthesis of 1,2-oxazine based derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazoles, 1-arylpiperazine and carbazoles. (4aR,8aR)-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[e][1,2]oxazine was found to be the most potent compound with a high degree of selectivity in

  在本研究中，我们使用固溶燃烧合成-氧化铋（Bi 2 O 3）作为催化剂，可以简单有效地合成基于1,2-恶嗪的6-氟-3-（哌啶丁-4-基）苯并衍生物。 [ d ]异恶唑，1-芳基哌嗪和咔唑。（4a R，8a R）-4-（4-甲氧基苯基）-3-（（（4-（4-甲氧基苯基）哌嗪-1-基）甲基）-4a，5,6,7,8,8a-六氢- 4 H-苯并[ e发现[] [1,2]恶嗪是最有效的化合物，对COX2（1.7μM）的抑制作用比对COX1（40.4μM）的抑制作用高，证明了1,2-恶嗪衍生物在开发COX2特异性抑制剂中的重要性。分子对接分析表明，COX1活性位点中的异亮氨酸残基负责降低与COX1的亲和力并提高对COX2的效力。总体而言，我们的研究表明，新的基于1,2-恶嗪的小分子在开发用于抗炎治疗的COX2特异性抑制剂中符合铅结构的条件。
• 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.