(R)-2-(1-hydroxy-3-methylbut-2-ylamino)-6-[3-(2-pyrimidinyl)phenylamino]-9-isopropylpurine | 1415505-36-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (R)-2-(1-hydroxy-3-methylbut-2-ylamino)-6-[3-(2-pyrimidinyl)phenylamino]-9-isopropylpurine
• 英文别名: (2R)-3-methyl-2-[[9-propan-2-yl-6-(3-pyrimidin-2-ylanilino)purin-2-yl]amino]butan-1-ol
• CAS: 1415505-36-0
• 化学式: C₂₃H₂₈N₈O
• 分子量: 432.528
• InChiKey: BPJMJPGXSGEUDV-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二氯-9-异丙基-9h-嘌呤 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 24.0h， 生成 (R)-2-(1-hydroxy-3-methylbut-2-ylamino)-6-[3-(2-pyrimidinyl)phenylamino]-9-isopropylpurine
  参考文献：
  名称：

  Synthesis and evaluation of new potent inhibitors of CK1 and CDK5, two kinases involved in Alzheimer’s disease

  摘要：

  Cyclin-dependent kinase 5 (CDK5) and Casein kinase 1 (CK1) are both involved in the hyperphosphorylation of the Tau protein and in the amyloid-beta production, the two major hallmarks of Alzheimer's disease. In the present paper, we describe the synthesis and biological evaluation of new series of 2,6,9-trisubstituted purines derived from DRF53, a dual specificity inhibitor of the kinase activity of CDK5 (IC50 = 80 nM) and CK1 (IC50 = 10 nM), and are able to prevent in a dose-dependent manner the CK1-dependent production of amyloid-beta in a cell model. Several molecules (e.g., 6e, 6g, 7c) displayed potent kinase inhibitory activities against CDK5 and CK1 (IC50 values ranging from 20 to 50 nM) among which a selective inhibitor of CK1 has been identified (5a, IC50 = 60 nM). In addition, some compounds exhibit sub-micromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer's disease (6g, IC50 = 510 nM).

  DOI：

  10.1007/s00044-012-0334-1

文献信息

• Synthesis and evaluation of new potent inhibitors of CK1 and CDK5, two kinases involved in Alzheimer’s disease
  作者：Luc Demange、Olivier Lozach、Yoan Ferandin、Nha Thu Hoang、Laurent Meijer、Hervé Galons

  DOI：10.1007/s00044-012-0334-1

  日期：2013.7

  Cyclin-dependent kinase 5 (CDK5) and Casein kinase 1 (CK1) are both involved in the hyperphosphorylation of the Tau protein and in the amyloid-beta production, the two major hallmarks of Alzheimer's disease. In the present paper, we describe the synthesis and biological evaluation of new series of 2,6,9-trisubstituted purines derived from DRF53, a dual specificity inhibitor of the kinase activity of CDK5 (IC50 = 80 nM) and CK1 (IC50 = 10 nM), and are able to prevent in a dose-dependent manner the CK1-dependent production of amyloid-beta in a cell model. Several molecules (e.g., 6e, 6g, 7c) displayed potent kinase inhibitory activities against CDK5 and CK1 (IC50 values ranging from 20 to 50 nM) among which a selective inhibitor of CK1 has been identified (5a, IC50 = 60 nM). In addition, some compounds exhibit sub-micromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer's disease (6g, IC50 = 510 nM).