N,N-dimethyl-2-(3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetamide | 26513-78-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: N,N-dimethyl-2-(3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetamide
• 英文别名: N,N-dimethyl-2-(3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-acetamide；N,N-dimethyl-2-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-yl)acetamide；N,N-dimethyl-2-(3-oxo-1,4-benzoxazin-4-yl)acetamide
• CAS: 26513-78-0
• 化学式: C₁₂H₁₄N₂O₃
• 分子量: 234.255
• InChiKey: YJUIUFBZJYDBFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-bromo-N-(2-hydroxyphenyl)acetamide 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N,N-dimethyl-2-(3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetamide
  参考文献：
  名称：

  Synthesis, biological activity and conformational study of 1,4-benzoxazine derivatives as potassium channel modulators

  摘要：

  With the aim of discovering new molecules with K+-channel activating properties, we have synthesized derivatives of cromakalim (CRK), an important molecule which shows specific affinity towards K+ channels, by replacing the benzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hydrophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the solid state conformation of these new molecules. When tested on rat aorta ring precontracted with phenylephrine, two compounds (2c and 2d) showed a concentration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80020-8

文献信息

• Development of Small-Molecule<i>Trypanosoma brucei N</i>-Myristoyltransferase Inhibitors: Discovery and Optimisation of a Novel Binding Mode
  作者：Daniel Spinks、Victoria Smith、Stephen Thompson、David A. Robinson、Torsten Luksch、Alasdair Smith、Leah S. Torrie、Stuart McElroy、Laste Stojanovski、Suzanne Norval、Iain T. Collie、Irene Hallyburton、Bhavya Rao、Stephen Brand、Ruth Brenk、Julie A. Frearson、Kevin D. Read、Paul G. Wyatt、Ian H. Gilbert

  DOI：10.1002/cmdc.201500301

  日期：2015.11

  bound in the previously reported active site, utilising a novel binding mode. This provides potential for further optimisation. The benzomorpholinone was also found to bind in a similar region. Using an X‐ray crystallography/structure‐based design approach, the benzomorpholinone series was further optimised, increasing activity against T. brucei NMT by >1000‐fold. A series of trypanocidal compounds were

  来自布氏锥虫的N-肉豆蔻酰转移酶(NMT)已在化学和生物学上被证实是人类非洲锥虫病的潜在药物靶点。我们之前报道了一些基于吡唑磺酰胺系列的非常有效的化合物的开发，这些化合物源自高通量筛选。在此，我们描述了在屏幕中也发现的噻唑烷酮和苯并吗啉支架的工作。大利什曼原虫中噻唑烷酮的 X 射线晶体结构NMT 利用一种新的结合模式显示了该化合物结合在先前报道的活性位点中。这提供了进一步优化的潜力。苯并吗啉酮也被发现在类似的区域结合。使用基于 X 射线晶体学/结构的设计方法，进一步优化了苯并吗啉酮系列，将抗布氏锥虫NMT 的活性提高了 1000 倍以上。确定了一系列具有合适体外 DMPK 特性的杀锥虫化合物，包括用于进一步开发的 CNS 暴露。需要进一步的工作来提高对人类 NMT 同种型的选择性和对布氏锥虫的活性。
• Synthesis, biological activity and conformational study of 1,4-benzoxazine derivatives as potassium channel modulators
  作者：Giuseppe Caliendo、Paolo Grieco、Elisa Perissutti、Vincenzo Santagada、Antonello Santini、Stefania Albrizio、Caterina Fattorusso、Aldo Pinto、Raffaella Sorrentino

  DOI：10.1016/s0223-5234(99)80020-8

  日期：1998.12

  With the aim of discovering new molecules with K+-channel activating properties, we have synthesized derivatives of cromakalim (CRK), an important molecule which shows specific affinity towards K+ channels, by replacing the benzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hydrophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the solid state conformation of these new molecules. When tested on rat aorta ring precontracted with phenylephrine, two compounds (2c and 2d) showed a concentration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug. (C) Elsevier, Paris.