(E)-N-(3,4-dimethylphenyl)-3-oxo-6-styryl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide | 1346113-80-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-N-(3,4-dimethylphenyl)-3-oxo-6-styryl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide
• 英文别名: NCGC00187737；N-(3,4-dimethylphenyl)-3-oxo-6-[(E)-2-phenylethenyl]-4H-1,4-benzoxazine-7-sulfonamide
• CAS: 1346113-80-1
• 化学式: C₂₄H₂₂N₂O₄S
• 分子量: 434.516
• InChiKey: PSQKROPAUXFMFR-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-bromo-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonyl chloride 在 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.33h， 生成 (E)-N-(3,4-dimethylphenyl)-3-oxo-6-styryl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide
  参考文献：
  名称：

  2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase

  摘要：

  Compared to normal differentiated cells, cancer cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is considerably less active and expressed in tumors. While the exact mechanism by which decreased pyruvate kinase activity contributes to anabolic metabolism remains unclear, it is hypothesized that activation of PKM2 to levels seen with PKM1 may promote a metabolic program that is not conducive to cell proliferation. Here we report the third chemotype in a series of PKM2 activators based on the 2-oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamide scaffold. The synthesis, structure activity relationships, selectivity and notable physiochemical properties are described. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.08.114

文献信息

• 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase
  作者：Martin J. Walsh、Kyle R. Brimacombe、Henrike Veith、James M. Bougie、Thomas Daniel、William Leister、Lewis C. Cantley、William J. Israelsen、Matthew G. Vander Heiden、Min Shen、Douglas S. Auld、Craig J. Thomas、Matthew B. Boxer

  DOI：10.1016/j.bmcl.2011.08.114

  日期：2011.11

  Compared to normal differentiated cells, cancer cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is considerably less active and expressed in tumors. While the exact mechanism by which decreased pyruvate kinase activity contributes to anabolic metabolism remains unclear, it is hypothesized that activation of PKM2 to levels seen with PKM1 may promote a metabolic program that is not conducive to cell proliferation. Here we report the third chemotype in a series of PKM2 activators based on the 2-oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamide scaffold. The synthesis, structure activity relationships, selectivity and notable physiochemical properties are described. Published by Elsevier Ltd.