6-[2-amino-6-(1-methylethyl)-4-pyrimidinyl]-1H-indazol-3-amine | 1271021-75-0

• 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: 6-[2-amino-6-(1-methylethyl)-4-pyrimidinyl]-1H-indazol-3-amine
• 英文别名: 6-(2-amino-6-propan-2-ylpyrimidin-4-yl)-1H-indazol-3-amine
• CAS: 1271021-75-0
• 化学式: C₁₄H₁₆N₆
• 分子量: 268.321
• InChiKey: VBJULRMRDQBSIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(2-Amino-6-propan-2-ylpyrimidin-4-yl)-2-fluorobenzonitrile 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 6-[2-amino-6-(1-methylethyl)-4-pyrimidinyl]-1H-indazol-3-amine
  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