(2S)-2-[[9-propan-2-yl-6-(pyrimidin-5-ylamino)purin-2-yl]amino]butan-1-ol | 1416987-42-2

• 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: (2S)-2-[[9-propan-2-yl-6-(pyrimidin-5-ylamino)purin-2-yl]amino]butan-1-ol
• CAS: 1416987-42-2
• 化学式: C₁₆H₂₂N₈O
• 分子量: 342.404
• InChiKey: ZPKXDHHDZZKMKI-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  (S)-(+)-2-氨基-1-丁醇 、 2-chloro-9-propan-2-yl-N-pyrimidin-5-ylpurin-6-amine 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 以60%的产率得到(2S)-2-[[9-propan-2-yl-6-(pyrimidin-5-ylamino)purin-2-yl]amino]butan-1-ol
  参考文献：
  名称：

  Potent inhibitors of CDK5 derived from roscovitine: Synthesis, biological evaluation and molecular modelling

  摘要：

  Cyclin dependent kinase 5 (CDK5) is a serine/threonine kinase belonging to the cyclin dependent kinase (CDK) family. CDK5 is involved in numerous neuronal diseases (including Alzheimer's or Parkinson's diseases, stroke, traumatic brain injury), pain signaling and cell migration. In the present Letter, we describe syntheses and biological evaluations of new 2,6,9-trisubstituted purines, structurally related to roscovitine, a promising CDK inhibitor currently in clinical trials (CDK1/Cyclin B, IC50 = 350 nM; CDK5/p25, IC50 = 200 nM). These new molecules were synthesized using an original Buchwald-Hartwig catalytic procedure; several compounds (3j, 3k, 3l, 3e, 4k, 6b, 6c) displayed potent kinase inhibitory potencies against CDK5 (IC50 values ranging from 17 to 50 nM) and showed significant cell death inducing activities (IC50 values ranging from 2 to 9 mu M on SH-SY5Y). The docking of the inhibitors into the ATP binding domain of the CDK5 catalytic site highlighted the discriminatory effect of a hydrogen bond involving the CDK5 Lys-89. In addition, the calculated final energy balances for complexation measured for several inhibitors is consistent with the ranking of the IC50 values. Lastly, we observed that several compounds exhibit submicromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer's disease (3g, 3h, 4m; IC50 values ranging from 300 to 400 nM). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.141

文献信息

• Potent inhibitors of CDK5 derived from roscovitine: Synthesis, biological evaluation and molecular modelling
  作者：Luc Demange、Fatma Nait Abdellah、Olivier Lozach、Yoan Ferandin、Nohad Gresh、Laurent Meijer、Hervé Galons

  DOI：10.1016/j.bmcl.2012.10.141

  日期：2013.1

  Cyclin dependent kinase 5 (CDK5) is a serine/threonine kinase belonging to the cyclin dependent kinase (CDK) family. CDK5 is involved in numerous neuronal diseases (including Alzheimer's or Parkinson's diseases, stroke, traumatic brain injury), pain signaling and cell migration. In the present Letter, we describe syntheses and biological evaluations of new 2,6,9-trisubstituted purines, structurally related to roscovitine, a promising CDK inhibitor currently in clinical trials (CDK1/Cyclin B, IC50 = 350 nM; CDK5/p25, IC50 = 200 nM). These new molecules were synthesized using an original Buchwald-Hartwig catalytic procedure; several compounds (3j, 3k, 3l, 3e, 4k, 6b, 6c) displayed potent kinase inhibitory potencies against CDK5 (IC50 values ranging from 17 to 50 nM) and showed significant cell death inducing activities (IC50 values ranging from 2 to 9 mu M on SH-SY5Y). The docking of the inhibitors into the ATP binding domain of the CDK5 catalytic site highlighted the discriminatory effect of a hydrogen bond involving the CDK5 Lys-89. In addition, the calculated final energy balances for complexation measured for several inhibitors is consistent with the ranking of the IC50 values. Lastly, we observed that several compounds exhibit submicromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer's disease (3g, 3h, 4m; IC50 values ranging from 300 to 400 nM). (C) 2012 Elsevier Ltd. All rights reserved.