2-(4-(溴甲基)苯基)-5-甲基吡啶 | 1119454-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-(4-(溴甲基)苯基)-5-甲基吡啶
• 英文名称: 2-(4-(Bromomethyl)phenyl)-5-methylpyridine
• 英文别名: 2-[4-(bromomethyl)phenyl]-5-methylpyridine
• CAS: 1119454-23-7
• 化学式: C₁₃H₁₂BrN
• 分子量: 262.149
• InChiKey: OGQKMBXHRGPLMT-UHFFFAOYSA-N

物化性质

• 沸点：
  359.3±30.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2-thiol 、 2-(4-(溴甲基)苯基)-5-甲基吡啶 在 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.25h， 以27%的产率得到2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(4-(5-methylpyridin-2-yl)benzylthio)-1,3,4-oxadiazole
  参考文献：
  名称：

  Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia

  摘要：

  The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML) may require alpha-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3 alpha selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3 alpha/beta with the highest GSK-3 alpha selectivity reported to dtae. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3 alpha targeting in AML cell lines was achieved with compound 27, resulting in a strong differrentiation phenotype and colony formation impairment, confirming the potential of GSK-3 alpha inhibition in AML therapy.

  DOI：

  10.1021/acs.jmedchem.5b01200
• 作为产物：
  描述：

  2-溴-5-甲基吡啶 在 四(三苯基膦)钯 、 三溴化磷 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 51.25h， 生成 2-(4-(溴甲基)苯基)-5-甲基吡啶
  参考文献：
  名称：

  Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia

  摘要：

  The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML) may require alpha-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3 alpha selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3 alpha/beta with the highest GSK-3 alpha selectivity reported to dtae. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3 alpha targeting in AML cell lines was achieved with compound 27, resulting in a strong differrentiation phenotype and colony formation impairment, confirming the potential of GSK-3 alpha inhibition in AML therapy.

  DOI：

  10.1021/acs.jmedchem.5b01200

文献信息

• Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia
  作者：Theresa Neumann、Lina Benajiba、Stefan Göring、Kimberly Stegmaier、Boris Schmidt

  DOI：10.1021/acs.jmedchem.5b01200

  日期：2015.11.25

  The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML) may require alpha-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3 alpha selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3 alpha/beta with the highest GSK-3 alpha selectivity reported to dtae. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3 alpha targeting in AML cell lines was achieved with compound 27, resulting in a strong differrentiation phenotype and colony formation impairment, confirming the potential of GSK-3 alpha inhibition in AML therapy.