4-hydroxy-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridine | 1236145-35-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-hydroxy-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridine
• 英文别名: 2-Oxa-11,17-diazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),3(8),4,6,12,14,16-heptaen-4-ol；2-oxa-11,17-diazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),3(8),4,6,12,14,16-heptaen-4-ol
• CAS: 1236145-35-9
• 化学式: C₁₄H₁₀N₂O₂
• 分子量: 238.246
• InChiKey: APTMWKZENIQFLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,3-二羟基苯甲醛 、 N-(氰甲基)氯化吡啶 以 水 为溶剂， 反应 14.5h， 以58%的产率得到4-hydroxy-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridine
  参考文献：
  名称：

  一锅法在水性介质中合成新型12 H -chromeno [2'，3'：4,5]咪唑并[1,2- a ]吡啶

  摘要：

  在包含水杨醛和1-（氰甲基）吡啶鎓氯化物的一锅缩合/环化反应中，在碳酸钠水溶液中生成了铬诺-咪唑并[1,2- a ]吡啶骨架。这些新型化合物的分离产率为47-71％。反应路径之后是1 H NMR光谱，可以清楚地了解该过程中涉及的副反应。 合成了不同的单取代吡啶鎓氯化物，并使其与单取代水杨醛反应，并对该合成方法的范围进行了详细讨论。

  DOI：

  10.1016/j.tet.2010.04.059

文献信息

• One-pot approach to the synthesis of novel 12H-chromeno[2′,3′:4,5]imidazo[1,2-a]pyridines in aqueous media
  作者：M. Fernanda Proença、Marta Costa

  DOI：10.1016/j.tet.2010.04.059

  日期：2010.6

  The chromeno-imidazo[1,2-a]pyridine scaffold was generated in an one pot condensation/cyclization reaction involving a salicylaldehyde and 1-(cyanomethyl)pyridinium chloride, in aqueous sodium carbonate solution. These novel compounds were isolated in 47–71% yield. The reaction pathway was followed by 1H NMR spectroscopy allowing a clear understanding of the side reactions involved in the process.

  在包含水杨醛和1-（氰甲基）吡啶鎓氯化物的一锅缩合/环化反应中，在碳酸钠水溶液中生成了铬诺-咪唑并[1,2- a ]吡啶骨架。这些新型化合物的分离产率为47-71％。反应路径之后是1 H NMR光谱，可以清楚地了解该过程中涉及的副反应。 合成了不同的单取代吡啶鎓氯化物，并使其与单取代水杨醛反应，并对该合成方法的范围进行了详细讨论。
• Novel structurally similar chromene derivatives with opposing effects on p53 and apoptosis mechanisms in colorectal HCT116 cancer cells
  作者：Cristovao F. Lima、Marta Costa、M.F. Proença、Cristina Pereira-Wilson

  DOI：10.1016/j.ejps.2015.02.019

  日期：2015.5

  In the present work, novel chromene derivatives fused with the imidazo[1,2-a]pyridine nucleus were tested for their anticancer potential in the human colorectal cancer HCT116 cells. Compounds 2a and 2c showed significant growth inhibitory activity with GI50 of 15 mu M and 11 mu M, respectively. Compound 2c, the most potent, has a carbamate group in position 8 of the pyridine ring, and showed significant cell cycle arrest and induction of cell death by apoptosis, even at 51xM. Besides different potencies, chromene analogs 2a and 2c showed different mechanisms of action. Whereas the carbamate-free chromene 2a induced cell cycle arrest at GI /G0 phase, compound 2c showed to arrest cell cycle at both S and G2 phases. Chromene derivative 2a at concentrations higher than its GI50 remarkably induced caspases-dependent apoptosis in a p53-independent manner. On the other hand, compound 2c increased significantly p53 levels and induced apoptosis in a p53- and caspases-dependent manner, even at concentrations lower than its GI50. Both compounds increased the Bax/Bcl-2 ratio, induced mitochondria depolarization and activated MAP kinases. In conclusion, two novel and structurally similar chromene derivatives showed cytotoxicity to HCT16 cells through opposing effects on p53 levels and apoptosis mechanisms, which may be relevant for further development of drugs acting on distinct molecular targets useful in the treatment of cancers with different genetic profiles and for personalized medicine. (C) 2015 Elsevier B.V. All rights reserved.