3-(2-((4-aminocyclohexyl)amino)-6-((4-(morpholinomethyl)phenyl)amino)-9H-purin-9-yl)propan-1-ol

• 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: 3-(2-((4-aminocyclohexyl)amino)-6-((4-(morpholinomethyl)phenyl)amino)-9H-purin-9-yl)propan-1-ol
• 化学式: C₂₅H₃₆N₈O₂
• 分子量: 480.613
• InChiKey: BHFNWJFWQLYFSY-XUTJKUGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.47
• 重原子数：
  35.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  126.38
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  3-(2,6-dichloro-9H-purin-9-yl)propan-1-ol 在 N,N-二异丙基乙胺 作用下， 以 丙醇 、 乙二醇 为溶剂， 反应 4.0h， 生成 3-(2-((4-aminocyclohexyl)amino)-6-((4-(morpholinomethyl)phenyl)amino)-9H-purin-9-yl)propan-1-ol
  参考文献：
  名称：

  Activity of 2,6,9-trisubstituted purines as potent PDGFRα kinase inhibitors with antileukaemic activity

  摘要：

  Receptor tyrosine kinase PDGFR alpha is often constitutively activated in various tumours and is regarded as a drug target. Here, we present a collection of 2,6,9-trisubstituted purines with nanomolar potency against PDGFR alpha and strong and selective cytotoxicity in the human eosinophilic leukaemia cell line EOL-1 that expresses the FIP1L1-PDGFRA oncogene. In treated EOL-1 cells, the example compound 14q inhibited the autophosphorylation of PDGFR alpha and the phosphorylation of STAT3 and ERK1/2. Interestingly, we observed pronounced and even increased effects of 14q on PDGFR alpha and some of its downstream signalling pathways after drug washout. In accordance with suppressed PDGFR alpha signalling, treated cells were arrested in the G1 phase of the cell cycle and eventually underwent apoptosis. Our results show that substituted purines can be used as specific modulators of eosinophilic leukaemia. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111663

文献信息

• Activity of 2,6,9-trisubstituted purines as potent PDGFRα kinase inhibitors with antileukaemic activity
  作者：Eva Řezníčková、Tomáš Gucký、Veronika Kováčová、Haresh Ajani、Radek Jorda、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2019.111663

  日期：2019.11

  Receptor tyrosine kinase PDGFR alpha is often constitutively activated in various tumours and is regarded as a drug target. Here, we present a collection of 2,6,9-trisubstituted purines with nanomolar potency against PDGFR alpha and strong and selective cytotoxicity in the human eosinophilic leukaemia cell line EOL-1 that expresses the FIP1L1-PDGFRA oncogene. In treated EOL-1 cells, the example compound 14q inhibited the autophosphorylation of PDGFR alpha and the phosphorylation of STAT3 and ERK1/2. Interestingly, we observed pronounced and even increased effects of 14q on PDGFR alpha and some of its downstream signalling pathways after drug washout. In accordance with suppressed PDGFR alpha signalling, treated cells were arrested in the G1 phase of the cell cycle and eventually underwent apoptosis. Our results show that substituted purines can be used as specific modulators of eosinophilic leukaemia. (C) 2019 Elsevier Masson SAS. All rights reserved.