2-(4-(5-nitropyridin-2-yl)piperazin-1-yl)ethan-1-ol | 747354-44-5

• 物质功能分类: 有机原料 - 醇、酚、酚醇类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(4-(5-nitropyridin-2-yl)piperazin-1-yl)ethan-1-ol
• 英文别名: 2-[4-(5-nitro-pyridin-2-yl)-piperazin-1-yl]-ethanol；2-[4-(5-Nitro-2-pyridinyl)piperazino]-1-ethanol；2-[4-(5-nitropyridin-2-yl)piperazin-1-yl]ethanol
• CAS: 747354-44-5
• 化学式: C₁₁H₁₆N₄O₃
• mdl: MFCD08692461
• 分子量: 252.273
• InChiKey: JNPCLGYWUHYNLR-UHFFFAOYSA-N

物化性质

• 熔点：
  102-105
• 沸点：
  469.8±45.0 °C(Predicted)
• 密度：
  1.307±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  85.4
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(4-(5-nitropyridin-2-yl)piperazin-1-yl)ethan-1-ol 在 盐酸 、 铁粉 、 对甲苯磺酸 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 27.0h， 生成  N-(2-((5-chloro-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors

  摘要：

  Aiming to develop promising ALK inhibitors, two series of N-2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 mu M. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALK(L1196M) with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.

  DOI：

  10.1016/j.bioorg.2018.09.019
• 作为产物：
  描述：

  N-羟乙基哌嗪 、 2-氯-5-硝基吡啶 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 以83.4%的产率得到2-(4-(5-nitropyridin-2-yl)piperazin-1-yl)ethan-1-ol
  参考文献：
  名称：

  Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors

  摘要：

  Aiming to develop promising ALK inhibitors, two series of N-2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 mu M. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALK(L1196M) with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.

  DOI：

  10.1016/j.bioorg.2018.09.019