(3S)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclopentyl-3-piperidinecarboxamide | 1271023-17-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: (3S)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclopentyl-3-piperidinecarboxamide
• 英文别名: (3S)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl]-N-cyclopentylpiperidine-3-carboxamide
• CAS: 1271023-17-6
• 化学式: C₂₂H₂₈N₈O
• 分子量: 420.517
• InChiKey: JBDVDZJOAKYYCL-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-溴-1H-吲唑-3-胺 在 4-二甲氨基吡啶 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 7.0h， 生成 (3S)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclopentyl-3-piperidinecarboxamide
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

  摘要：

  Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDKI might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDKI inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OC1-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDKI and the potential pharmacological uses of a PDK1 inhibitor.

  DOI：

  10.1021/jm101527u