(R)-2-(1-hydroxy-3-methylbut-2-ylamino)-6-[4-(2-pyridyl)phenylmethylamino]-9-iso-propylpurine | 1056016-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-2-(1-hydroxy-3-methylbut-2-ylamino)-6-[4-(2-pyridyl)phenylmethylamino]-9-iso-propylpurine
• 英文别名: (2R)-3-methyl-2-[[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]amino]butan-1-ol
• CAS: 1056016-22-8
• 化学式: C₂₅H₃₁N₇O
• 分子量: 445.567
• InChiKey: KORMOHIBSWURFV-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  D-缬氨醇 、 2-chloro-9-isopropyl-N-[[4-(2-pyridyl)phenyl]methyl]purin-6-amine 在 三正丁胺 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 以76%的产率得到(R)-2-(1-hydroxy-3-methylbut-2-ylamino)-6-[4-(2-pyridyl)phenylmethylamino]-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

文献信息

• USE OF PURINE DERIVATIVES FOR THE MANUFACTURE OF A MEDICAMENT
  申请人：Meijer Laurent

  公开号：US20100311768A1

  公开（公告）日：2010-12-09

  The invention relates to the use of purine derivatives in the manufacture of a medicament for treating pathological conditions in which an imbalance between cell division and apoptosis is involved, and more particularly in which excessive apoptosis is responsible for the pathological condition. According to the invention, a purine derivative of formula I is used. The invention finds use in the pharmaceutical field.

  本发明涉及使用嘌呤衍生物制造药物，用于治疗细胞分裂和凋亡失衡所涉及的病理状况，尤其是过度凋亡导致病理状况的情况。根据本发明，使用式I的嘌呤衍生物。本发明在制药领域中得到应用。
• UTILISATION DE DERIVES DE PURINE POUR LA FABRICATION D'UN MEDICAMENT
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2187889B1

  公开（公告）日：2013-11-06
• US8431583B2
  申请人：——

  公开号：US8431583B2

  公开（公告）日：2013-04-30
• [EN] USE OF PURINE DERIVATIVES FOR THE MANUFACTURE OF A MEDICAMENT<br/>[FR] UTILISATION DE DERIVES DE PURINE POUR LA FABRICATION D'UN MEDICAMENT
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2009068761A2

  公开（公告）日：2009-06-04

  L'invention concerne l'utilisation de dérivés de purine dans la fabrication d'un médicament pour traiter les pathologies dans lesquelles un déséquilibre entre division cellulaire et apoptose est impliqué et plus particulièrement dans laquelle une apoptose excessive est à l'origine de la pathologie. Selon l'invention, un dérivé de purine de formule I est utilisé. L'invention trouve application dans le domaine pharmaceutique.
• Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1
  作者：Nassima Oumata、Karima Bettayeb、Yoan Ferandin、Luc Demange、Angela Lopez-Giral、Marie-Lorène Goddard、Vassilios Myrianthopoulos、Emmanuel Mikros、Marc Flajolet、Paul Greengard、Laurent Meijer、Hervé Galons

  DOI：10.1021/jm800109e

  日期：2008.9.11

  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.