6-(methylthio)-1-(spiro[2.5]octan-6-yl)-1H-pyrazolo[3,4-d]pyrimidine | 1365169-98-7

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 6-(methylthio)-1-(spiro[2.5]octan-6-yl)-1H-pyrazolo[3,4-d]pyrimidine
• CAS: 1365169-98-7
• 化学式: C₁₄H₁₈N₄S
• 分子量: 274.39
• InChiKey: VMWVWZROAYDUEE-UHFFFAOYSA-N

物化性质

• 沸点：
  480.6±37.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  43.6
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  6-(methylthio)-1-(spiro[2.5]octan-6-yl)-1H-pyrazolo[3,4-d]pyrimidine 在 吡啶 、 甲醇 、 二碳酸二叔丁酯 、 碳酸氢铵 、 potassium carbonate 、 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 1-Methyl-4-[(1-spiro[2.5]octan-6-ylpyrazolo[3,4-d]pyrimidin-6-yl)amino]pyrrole-2-carboxamide
  参考文献：
  名称：

  Synthesis, SAR and biological evaluation of 1,6-disubstituted-1H-pyrazolo[3,4-d]pyrimidines as dual inhibitors of Aurora kinases and CDK1

  摘要：

  Since the early 2000s, the Aurora kinases have become major targets of oncology drug discovery particularly Aurora-A and Aurora-B kinases (AKA/AKB) for which the selective inhibition in cells lead to different phenotypes. In addition to targeting these Aurora kinases involved in mitosis, CDK1 has been added as a primary inhibition target in hopes of enhancing the cytotoxicity of our chemotypes harboring the pyrazolopyrimidine core. SAR optimization of this series using the AKA, AKB and CDK1 biochemical assays led to the discovery of the compound 7h which combines strong potency against the 3 kinases with an acceptable microsomal stability. Finally, switching from a primary amide to a two-substituted pyrrolidine amide gave rise to compound 15a which exhibited the desired AKA/CDK1 inhibition phenotype in cells but showed moderate activity in animal models using HCT116 tumor cell lines. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.019
• 作为产物：
  描述：

  6-羟基螺[2.5]辛烷 、 6-(甲基硫代)-1H-吡唑并[3,4-d]嘧啶 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 6-(methylthio)-1-(spiro[2.5]octan-6-yl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Synthesis, SAR and biological evaluation of 1,6-disubstituted-1H-pyrazolo[3,4-d]pyrimidines as dual inhibitors of Aurora kinases and CDK1

  摘要：

  Since the early 2000s, the Aurora kinases have become major targets of oncology drug discovery particularly Aurora-A and Aurora-B kinases (AKA/AKB) for which the selective inhibition in cells lead to different phenotypes. In addition to targeting these Aurora kinases involved in mitosis, CDK1 has been added as a primary inhibition target in hopes of enhancing the cytotoxicity of our chemotypes harboring the pyrazolopyrimidine core. SAR optimization of this series using the AKA, AKB and CDK1 biochemical assays led to the discovery of the compound 7h which combines strong potency against the 3 kinases with an acceptable microsomal stability. Finally, switching from a primary amide to a two-substituted pyrrolidine amide gave rise to compound 15a which exhibited the desired AKA/CDK1 inhibition phenotype in cells but showed moderate activity in animal models using HCT116 tumor cell lines. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.019