N-(4-acetylphenyl)-2-oxo-1,2,3,4-tetrahydroquinoline-6-sulfonamide | 878949-48-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-acetylphenyl)-2-oxo-1,2,3,4-tetrahydroquinoline-6-sulfonamide
• 英文别名: N-(4-acetylphenyl)-2-oxo-3,4-dihydro-1H-quinoline-6-sulfonamide
• CAS: 878949-48-5
• 化学式: C₁₇H₁₆N₂O₄S
• 分子量: 344.391
• InChiKey: XVGKCUDOPBHEKH-UHFFFAOYSA-N

物化性质

• 溶解度：
  48.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-acetylphenyl)-2-oxo-1,2,3,4-tetrahydroquinoline-6-sulfonamide 在 phenyltrimethylammonium tribromide 、 三乙胺 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 16.58h， 生成 N-(4-(4-hydroxy-3-(pyridin-3-ylmethyl)-2-thioxothiazolidin-4-yl)phenyl)-2-oxo-1,2,3,4-tetrahydroquinoline-6-sulfonamide
  参考文献：
  名称：

  Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators

  摘要：

  Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 mu M to 0.81 mu M against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.023
• 作为产物：
  描述：

  4-氨基苯乙酮 、 1,2,3,4-四氢-2-氧代-6-喹啉磺酰氯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以91%的产率得到N-(4-acetylphenyl)-2-oxo-1,2,3,4-tetrahydroquinoline-6-sulfonamide
  参考文献：
  名称：

  Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators

  摘要：

  Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 mu M to 0.81 mu M against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.023