5,7-dimethoxy-2-(4-nitrophenyl)imidazo[1,2-a]pyrimidine | 1620909-93-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5,7-dimethoxy-2-(4-nitrophenyl)imidazo[1,2-a]pyrimidine
• 英文别名: 5,7-Dimethoxy-2-(4-nitrophenyl)imidazo[1,2-a]pyrimidine
• CAS: 1620909-93-4
• 化学式: C₁₄H₁₂N₄O₄
• 分子量: 300.274
• InChiKey: MFHYWZRXKNCMAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  94.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,7-dimethoxy-2-(4-nitrophenyl)imidazo[1,2-a]pyrimidine 在 tin(ll) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以77%的产率得到4-(5,7-dimethoxyimidazo[1,2-a]pyrimidin-2-yl)aniline
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines as new inhibitors of the Wnt/β-catenin signaling

  摘要：

  Wnt/β-catenin signaling plays an important role in the regulation of embryonic development and tumorigenesis. Since its deregulation results in severe human diseases, especially cancer, the Wnt signaling pathway constitutes a promising platform for pharmacological targeting of cancer. In this study we synthesized a series of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines and identified some derivatives that were able to inhibit the Wnt/β-catenin signaling pathway in a luciferase reporter assay and cell proliferation in selected cancer cell lines, endowed with APC or β-catenin gene mutations. The most active compounds significantly downregulate the expression of Wnt target genes such as c-myc and cyclin D1. Further studies indicated that these compounds function independently of GSK-3β activity. More importantly, in vivo experiments, carried out on a Wnt-reporter zebrafish model indicate, in particular for compounds 4c and 4i as the most active compounds, an activity comparable to that of the reference compound IWR1, suggesting their potential use not only as small molecule inhibitors of the Wnt/β-catenin signal in Wnt driven cancers, but also in other Wnt-related diseases.

  DOI：

  10.1016/j.ejmech.2014.05.071
• 作为产物：
  描述：

  2-氨基-4,6-二甲氧基嘧啶 、 2-溴-4'-硝基苯乙酮 以 乙醇 为溶剂， 以82%的产率得到5,7-dimethoxy-2-(4-nitrophenyl)imidazo[1,2-a]pyrimidine
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines as new inhibitors of the Wnt/β-catenin signaling

  摘要：

  Wnt/β-catenin signaling plays an important role in the regulation of embryonic development and tumorigenesis. Since its deregulation results in severe human diseases, especially cancer, the Wnt signaling pathway constitutes a promising platform for pharmacological targeting of cancer. In this study we synthesized a series of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines and identified some derivatives that were able to inhibit the Wnt/β-catenin signaling pathway in a luciferase reporter assay and cell proliferation in selected cancer cell lines, endowed with APC or β-catenin gene mutations. The most active compounds significantly downregulate the expression of Wnt target genes such as c-myc and cyclin D1. Further studies indicated that these compounds function independently of GSK-3β activity. More importantly, in vivo experiments, carried out on a Wnt-reporter zebrafish model indicate, in particular for compounds 4c and 4i as the most active compounds, an activity comparable to that of the reference compound IWR1, suggesting their potential use not only as small molecule inhibitors of the Wnt/β-catenin signal in Wnt driven cancers, but also in other Wnt-related diseases.

  DOI：

  10.1016/j.ejmech.2014.05.071

文献信息

• Synthesis and biological evaluation of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines as new inhibitors of the Wnt/β-catenin signaling
  作者：Barbara Cosimelli、Sonia Laneri、Carmine Ostacolo、Antonia Sacchi、Elda Severi、Elena Porcù、Elena Rampazzo、Enrico Moro、Giuseppe Basso、Giampietro Viola

  DOI：10.1016/j.ejmech.2014.05.071

  日期：2014.8

  Wnt/β-catenin signaling plays an important role in the regulation of embryonic development and tumorigenesis. Since its deregulation results in severe human diseases, especially cancer, the Wnt signaling pathway constitutes a promising platform for pharmacological targeting of cancer. In this study we synthesized a series of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines and identified some derivatives that were able to inhibit the Wnt/β-catenin signaling pathway in a luciferase reporter assay and cell proliferation in selected cancer cell lines, endowed with APC or β-catenin gene mutations. The most active compounds significantly downregulate the expression of Wnt target genes such as c-myc and cyclin D1. Further studies indicated that these compounds function independently of GSK-3β activity. More importantly, in vivo experiments, carried out on a Wnt-reporter zebrafish model indicate, in particular for compounds 4c and 4i as the most active compounds, an activity comparable to that of the reference compound IWR1, suggesting their potential use not only as small molecule inhibitors of the Wnt/β-catenin signal in Wnt driven cancers, but also in other Wnt-related diseases.