2-氯-6-[4-(4-吡啶基)苯基氨基]-9-异丙基嘌呤 | 1056016-79-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氯-6-[4-(4-吡啶基)苯基氨基]-9-异丙基嘌呤
• 英文名称: 2-chloro-6-[4-(4-pyridyl)phenylamino]-9-iso-propylpurine
• CAS: 1056016-79-5
• 化学式: C₁₉H₁₇ClN₆
• 分子量: 364.837
• InChiKey: VXFSDBNDQKQWGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  68.52
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-氨基丁醇 、 2-氯-6-[4-(4-吡啶基)苯基氨基]-9-异丙基嘌呤 在 三正丁胺 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 以37%的产率得到(R)-2-(1-hydroxy-but-2-ylamino)-6-[4-(4-pyridyl)phenylamino]-9-iso-propylpurine
  参考文献：
  名称：

  Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1

  摘要：

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.

  DOI：

  10.1021/jm800109e
• 作为产物：
  描述：

  4-溴吡啶 、 2-氯-9-(1-甲基乙基)-N-[4-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苯基]-9H-嘌呤-6-胺 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以70%的产率得到2-氯-6-[4-(4-吡啶基)苯基氨基]-9-异丙基嘌呤
  参考文献：
  名称：

  Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1

  摘要：

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.

  DOI：

  10.1021/jm800109e