6-(4-(2,6-difluorophenylsulfonyl)piperazin-1-ylsulfonyl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine | 1203493-82-6

• 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-(4-(2,6-difluorophenylsulfonyl)piperazin-1-ylsulfonyl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine
• 英文别名: 6-[4-(2,6-Difluorophenyl)sulfonylpiperazin-1-yl]sulfonyl-4-methyl-2,3-dihydro-1,4-benzoxazine
• CAS: 1203493-82-6
• 化学式: C₁₉H₂₁F₂N₃O₅S₂
• 分子量: 473.522
• InChiKey: DXQBRDXSUQRLIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪-6-磺酰氯 、 tert-butyl 4-[(2,6-difluorobenzene)sulfonyl]piperazine-1-carboxylate trifluoroacetate salt 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 6-(4-(2,6-difluorophenylsulfonyl)piperazin-1-ylsulfonyl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine
  参考文献：
  名称：

  Evaluation of Substituted N,N′-Diarylsulfonamides as Activators of the Tumor Cell Specific M2 Isoform of Pyruvate Kinase

  摘要：

  The metabolism of cancer cells is altered to support rapid proliferation. Pharmacological activators of a tumor cell specific pyruvate kinase isozyme (PKM2) may be an approach for altering the classic Warburg effect characteristic of aberrant metabolism in cancer cells yielding a novel anti proliferation strategy. In this manuscript, we detail the discovery of a series of Substituted N,N'-diarylsulfonamides as activators of PKM2. The synthesis of numerous analogues and the evaluation of structure-activity relationships are presented as well as assessments of mechanism and selectivity. Several agents are found that have good potencies and appropriate solubility for use as chemical probes of PKM2 including 55 (AC(50) = 43 nM, maximum response = 84%; solubility = 7.3 mu g/mL), 56 (AC(50) = 99 nM, maximum response 84%; solubility = 5.7 mu g/mL), and 58 (AC(50) = 38 nM, maximum response = 82%; solubility 51.2 mu g/mL). The small molecules described here represent first-in-class activators of PKM2

  DOI：

  10.1021/jm901577g

文献信息

• ACTIVATORS OF HUMAN PYRUVATE KINASE
  申请人：Thomas Craig J.

  公开号：US20120245141A1

  公开（公告）日：2012-09-27

  Disclosed are pyruvate kinase M2 activators, which are, bis sulfonamide piperazinyl compounds of Formula (I) and 2,4-disubstituted 4H-thieno[3,2-b]pyrrole-2-(substituted benzyl)pyridazin-3(2H)ones of Formula (II), wherein L and R 1 to R 16 are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer and anemia,

  本发明涉及丙酮酸激酶M2激活剂，其为式（I）的双磺酰胺哌嗪化合物和式（II）的2,4-二取代4H-噻吩[3,2-b]吡咯-2-(取代苄基)吡啶并[3(2H)]酮，其中L和R1至R16如本文所定义，可用于治疗许多可通过激活PKM2治疗的疾病，例如癌症和贫血。
• PYRUVATE KINASE ACTIVATORS FOR USE FOR INCREASING LIFETIME OF THE RED BLOOD CELLS AND TREATING ANEMIA
  申请人：Agios Pharmaceuticals, Inc.

  公开号：EP2704719A1

  公开（公告）日：2014-03-12
• METHODS OF USING PYRUVATE KINASE ACTIVATORS
  申请人：Su Shin-San M.

  公开号：US20140148444A1

  公开（公告）日：2014-05-29

  Described herein are compounds that activate pyruvate kinase, for use in a method for increasing lifetime of the red blood cells, for regulating 2,3-diphosphoglycerate levels in blood and for treating sickle cell anemia.
• US8841305B2
  申请人：——

  公开号：US8841305B2

  公开（公告）日：2014-09-23
• US8937067B2
  申请人：——

  公开号：US8937067B2

  公开（公告）日：2015-01-20