2-(benzylthio)-6-isobutoxypyrimidin-4-amine | 1620909-67-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(benzylthio)-6-isobutoxypyrimidin-4-amine
• 英文别名: 2-Benzylsulfanyl-6-(2-methylpropoxy)pyrimidin-4-amine；2-benzylsulfanyl-6-(2-methylpropoxy)pyrimidin-4-amine
• CAS: 1620909-67-2
• 化学式: C₁₅H₁₉N₃OS
• 分子量: 289.401
• InChiKey: OIJKJZPCNCXNCF-UHFFFAOYSA-N

物化性质

• 熔点：
  88.3-89 °C
• 沸点：
  477.3±35.0 °C(predicted)
• 密度：
  1.19±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(benzylthio)-6-isobutoxypyrimidin-4-amine 、 乙酰氯 以 四氢呋喃 为溶剂， 反应 4.0h， 以58%的产率得到N-[2-(benzylthio)-6-isobutoxypyrimidin-4-yl]acetamide
  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：

  溴甲苯 在 potassium carbonate 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-(benzylthio)-6-isobutoxypyrimidin-4-amine
  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

• 4-amino-6-alkyloxy-2-alkylthiopyrimidine derivatives as novel non-nucleoside agonists for the adenosine A₁receptor
  作者：Barbara Cosimelli、Giovanni Greco、Sonia Laneri、Ettore Novellino、Antonia Sacchi、Maria Letizia Trincavelli、Chiara Giacomelli、Sabrina Taliani、Federico Da Settimo、Claudia Martini

  DOI：10.1111/cbdd.12801

  日期：2016.11

  non-nucleoside agonists at human adenosine receptors (ARs). When tested in competition binding experiments, these compounds exhibited low micromolar affinity (Ki values comprised between 1.2 and 1.9 mum) for the A1 AR and no appreciable affinity for the A2A and A3 ARs. Evaluation of their efficacy profiles by measurement of intracellular cAMP levels revealed that 4 and 5 behave as non-nucleoside agonists of the

  研究了三种4-氨基-6-烷氧基-2-烷基硫代嘧啶衍生物（4-6）作为人腺苷受体（ARs）的潜在非核苷激动剂。当在竞争结合实验中测试时，这些化合物对A1 AR表现出低的微摩尔亲和力（Ki值介于1.2和1.9微米之间），对A2A和A3 ARs没有明显的亲和力。通过测量细胞内cAMP水平评估其功效谱显示，有4和5表现为A1 AR的非核苷激动剂，其EC50值分别为0.47和0.87微米。替代地，无法获得清晰的6浓度响应曲线，这可能是因为该化合物调节了一个或多个其他靶标，从而掩盖了其活化A1 AR所产生的推定效应。
• 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.