6-bromo-N-(3,4-dimethylphenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide | 1345822-42-5

• 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: 6-bromo-N-(3,4-dimethylphenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide
• 英文别名: 6-bromo-N-(3,4-dimethylphenyl)-3-oxo-4H-1,4-benzoxazine-7-sulfonamide
• CAS: 1345822-42-5
• 化学式: C₁₆H₁₅BrN₂O₄S
• 分子量: 411.276
• InChiKey: UKDWCJDLGFLUDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-bromo-N-(3,4-dimethylphenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide 、 反式-BETA-苯乙烯硼酸 在 sodium carbonate 作用下， 以 水 、 1,2-二氯乙烷 为溶剂， 反应 0.33h， 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
• 作为产物：
  描述：

  6-bromo-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonyl chloride 、 3,4-二甲基苯胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 6-bromo-N-(3,4-dimethylphenyl)-3-oxo-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

• [EN] DIHYDROBENZOXAZINE AND TETRAHYDROQUINOXALINE SODIUM CHANNEL INHIBITORS<br/>[FR] INHIBITEURS DES CANAUX SODIQUES DE TYPE DIHYDROBENZOXAZINE ET TÉTRAHYDROQUINOXALINE
  申请人：AMGEN INC

  公开号：WO2013122897A1

  公开（公告）日：2013-08-22

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了式I的化合物或其药学上可接受的盐，这些化合物是电压门控钠通道的抑制剂，特别是Nav 1.7。这些化合物对于治疗可通过抑制钠通道治疗的疾病，如疼痛障碍，是有用的。还提供了含有本发明化合物的药物组合物。
• [EN] ACTIVATORS OF HUMAN PYRUVATE KINASE<br/>[FR] ACTIVATEURS DE LA PYRUVATE KINASE HUMAINE
  申请人：US HEALTH

  公开号：WO2011137089A1

  公开（公告）日：2011-11-03

  Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A1, A2, L, R, R1 to R3, X1 to X3, k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A1 -NR-L-A2 (I)

  公开了一些丙酮酸激酶M2激活剂，这些激活剂是化合物式(I)的化合物，包括化合物式(II)，其中A1、A2、L、R、R1至R3、X1至X3、k、n和m的定义如下，在治疗通过激活PKM2可治疗的多种疾病中有用，例如癌症。 A1 -NR-L-A2 (I)
• ACTIVATORS OF HUMAN PYRUVATE KINASE
  申请人：Boxer Matthew B.

  公开号：US20130109672A1

  公开（公告）日：2013-05-02

  Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A 1 , A 2 , L, R, R 1 to R 3 , X 1 to X 3 , k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A 1 -NR-L-A 2 (I).

  本发明涉及一种丙酮酸激酶M2活化剂，包括式(I)中的化合物，其中包括式(II)中的化合物，其中A1、A2、L、R、R1到R3、X1到X3、k、n和m的定义如本文所述，这些化合物可用于治疗许多可通过激活PKM2来治疗的疾病，例如癌症。其中，A1-NR-L-A2(I)。
• DIHYDROBENZOXAZINE AND TETRAHYDROQUINOXALINE SODIUM CHANNEL INHIBITORS
  申请人：AMGEN INC.

  公开号：US20150057271A1

  公开（公告）日：2015-02-26

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了I式化合物或其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav1.7。这些化合物对于治疗可通过钠通道抑制治疗的疾病如疼痛症状是有用的。还提供了含有本发明化合物的药物组合物。
• US9346798B2
  申请人：——

  公开号：US9346798B2

  公开（公告）日：2016-05-24