3-[2-amino-5-(trifluoromethoxy)phenyl]-1H-quinoxalin-2-one | 312723-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-[2-amino-5-(trifluoromethoxy)phenyl]-1H-quinoxalin-2-one
• CAS: 312723-92-5
• 化学式: C₁₅H₁₀F₃N₃O₂
• 分子量: 321.259
• InChiKey: FORPSKNLFJONIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  邻苯二胺 、 5-三氟甲氧基吲哚-2,3-二酮 在 potassium hydroxide 作用下， 以 水 为溶剂， 生成 3-[2-amino-5-(trifluoromethoxy)phenyl]-1H-quinoxalin-2-one
  参考文献：
  名称：

  A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells

  摘要：

  The KRAS oncogene is found in up to 30% of all human tumors. In 2009, RNAi experiments revealed that lowering mRNA levels of a transcript encoding the serine/threonine kinase STK33 was selectively toxic to KRAS-dependent cancer cell lines, suggesting that small-molecule inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Molecular Libraries Small Molecule Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chemical probe ML281 that showed low nanomolar inhibition of purified recombinant STK33 and a distinct selectivity profile as compared to other STK33 inhibitors that were reported in the course of these studies. Even at the highest concentration tested (10 mu M), ML281 had no effect on the viability of KRAS-dependent cancer cells. These results are consistent with other recent reports using small-molecule STK33 inhibitors. Small molecules having different chemical structures and kinase-selectivity profiles are needed to fully understand the role of STK33 in KRAS-dependent cancers. In this regard, ML281 is a valuable addition to small-molecule probes of STK33.

  DOI：

  10.1021/ml300246r

文献信息

• A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells
  作者：Michel Weïwer、James Spoonamore、Jingqiang Wei、Boris Guichard、Nathan T. Ross、Kristina Masson、Whitney Silkworth、Sivaraman Dandapani、Michelle Palmer、Christina A. Scherer、Andrew M. Stern、Stuart L. Schreiber、Benito Munoz

  DOI：10.1021/ml300246r

  日期：2012.12.13

  The KRAS oncogene is found in up to 30% of all human tumors. In 2009, RNAi experiments revealed that lowering mRNA levels of a transcript encoding the serine/threonine kinase STK33 was selectively toxic to KRAS-dependent cancer cell lines, suggesting that small-molecule inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Molecular Libraries Small Molecule Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chemical probe ML281 that showed low nanomolar inhibition of purified recombinant STK33 and a distinct selectivity profile as compared to other STK33 inhibitors that were reported in the course of these studies. Even at the highest concentration tested (10 mu M), ML281 had no effect on the viability of KRAS-dependent cancer cells. These results are consistent with other recent reports using small-molecule STK33 inhibitors. Small molecules having different chemical structures and kinase-selectivity profiles are needed to fully understand the role of STK33 in KRAS-dependent cancers. In this regard, ML281 is a valuable addition to small-molecule probes of STK33.