2-chloro-9-isopropyl-N-[[4-(2-pyridyl)phenyl]methyl]purin-6-amine | 294648-01-4

• 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: 2-chloro-9-isopropyl-N-[[4-(2-pyridyl)phenyl]methyl]purin-6-amine
• 英文别名: 2-chloro-9-propan-2-yl-N-[(4-pyridin-2-ylphenyl)methyl]purin-6-amine
• CAS: 294648-01-4
• 化学式: C₂₀H₁₉ClN₆
• 分子量: 378.864
• InChiKey: AOPLJKWUEJZIPY-UHFFFAOYSA-N

物化性质

• 熔点：
  178-179 °C
• 沸点：
  538.1±60.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• pKa：
  4.51±0.25 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氨基丁醇 、 2-chloro-9-isopropyl-N-[[4-(2-pyridyl)phenyl]methyl]purin-6-amine 反应 8.0h， 以92%的产率得到(2R)-2-[[9-异丙基-6-[[[4-(2-吡啶基)苯基]甲基]氨基]-9H-嘌呤-2-基]氨基]-1-丁醇
  参考文献：
  名称：

  Practical Synthesis of Roscovitine and CR8

  摘要：

  Roscovitine and CR8 are potent inhibitors of cyclin-dependent kinases. A scalable synthesis of both inhibitors is described. In the case of CR8, the biarylmethylamine moiety was obtained as a stable and high-purity salt.

  DOI：

  10.1021/op800284k
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 potassium carbonate 、 三乙胺 作用下， 以 二甲基亚砜 、 正丁醇 为溶剂， 反应 2.0h， 生成 2-chloro-9-isopropyl-N-[[4-(2-pyridyl)phenyl]methyl]purin-6-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of selective and potent cyclin-dependent kinase inhibitors

  摘要：

  A new series of 2,6,9-trisubstituted purines, structurally related to the cyclin-dependent kinase (CDK) inhibitor Roscovitine, has been synthesized. These compounds mainly differ by the substituent on the C-2 position which encompasses a diol group. These compounds were screened for kinase inhibitory activities and antiproliferative effects. They were shown to be potent inhibitors of cyclin-dependent kinases but also, for some of them of casein kinase 1 (CK1) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). The inhibition of kinases was accompanied by an antiproliferative effect against several tumor cell-lines. The most potent derivatives inhibited SH-SY5Y (neuroblastoma) tumor cell line with an IC50 < 0.5 mu M which means approximately a 30 fold increase compared to Roscovitine. A valine ester was also prepared from the most potent inhibitor to serve as a prodrug. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.033

文献信息

• [EN] METHOD OF TREATMENT OF POLYCYSTIC DISEASES AND CHRONIC LYMPHOCYTIC LEUKEMIA<br/>[FR] PROCÉDÉ DE TRAITEMENT DES MALADIES POLYKYSTIQUES ET DE LA LEUCÉMIE LYMPHOCYTAIRE CHRONIQUE
  申请人：CHU DE BREST

  公开号：WO2010103473A1

  公开（公告）日：2010-09-16

  The present invention concerns a method of treatment of polycystic diseases or of reducing and/or avoiding cyst formation in a patient with cystic disease, which comprises at least one step consisting in administering to said patient an effective amount of a 2,6,9-trisubstituted purine compound of formula (VII): wherein A represents alternatively a (A.1) or (A.2) group.

  本发明涉及一种治疗多囊疾病或减少和/或避免囊肿形成的方法，包括至少一步，即向患有囊性疾病的患者施用有效量的式（VII）的2,6,9-三取代嘌呤化合物的方法：其中A代表可选择的（A.1）或（A.2）基团。
• 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。
• 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.
• UTILISATION DE DERIVES DE PURINE POUR LA FABRICATION D'UN MEDICAMENT
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2187889A2

  公开（公告）日：2010-05-26
• US8431583B2
  申请人：——

  公开号：US8431583B2

  公开（公告）日：2013-04-30