(2-Chloro-9H-purin-6-yl)-(3-nitro-phenyl)-amine | 482615-27-0

• 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: (2-Chloro-9H-purin-6-yl)-(3-nitro-phenyl)-amine
• 英文别名: 2-chloro-N-(3-nitrophenyl)-7H-purin-6-amine
• CAS: 482615-27-0
• 化学式: C₁₁H₇ClN₆O₂
• 分子量: 290.669
• InChiKey: CHOHUTWWDHJALH-UHFFFAOYSA-N

物化性质

• 密度：
  1.696±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2-Chloro-9H-purin-6-yl)-(3-nitro-phenyl)-amine 在 potassium carbonate 作用下， 以 二乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 trans-4-[9-ethyl-6-(3-nitro-phenylamino)-9H-purin-2-yl-amino]cyclohexanol
  参考文献：
  名称：

  Potent and orally active purine-based fetal hemoglobin inducers for treating β-thalassemia and sickle cell disease

  摘要：

  Reactivation of fetal hemoglobin (HbF) expression by therapeutic agents has been suggested as an alternative treatment to modulate anemia and the related symptoms of severe β-thalassemia and sickle cell disease (SCD). Hydroxyurea (HU) is the first US FDA-approved HbF inducer for treating SCD. However, approximately 25% of the patients with SCD do not respond to HU. A previous study identified TN1 (1) as a small-molecule HbF inducer. However, this study found that the poor potency and oral bioavailability of compound 1 limits the development of this inducer for clinical use. To develop drug-like compounds, further structure-activity relationship studies on the purine-based structure of 1 were conducted. Herein, we report our discovery of a more potent inducer, compound 13a, that can efficiently induce γ-globin gene expression at non-cytotoxic concentrations. The molecular mechanism of 13a, for the regulation HbF expression, was also investigated. In addition, we demonstrated that oral administration of 13a can ameliorate anemia and the related symptoms in SCD mice. The results of this study suggest that 13a can be further developed as a novel agent for treating hemoglobinopathies, such as β-thalassemia and SCD.

  DOI：

  10.1016/j.ejmech.2020.112938
• 作为产物：
  描述：

  2,6-二氯嘌呤 、 间硝基苯胺 在 氮气 、 乙醚 、 水 、 disodium;carbonate 作用下， 以 戊醇 、 乙醚 为溶剂， 反应 2.0h， 以to afford the title compound as a lemon-yellow powder (1.01 g, quant.)的产率得到(2-Chloro-9H-purin-6-yl)-(3-nitro-phenyl)-amine
  参考文献：
  名称：

  2,6,9-substituted purine derivatives and their use in the treatment of proliferative disorders

  摘要：

  本发明涉及式I的化合物或其药学上可接受的盐，其中： R2为2-羟甲基吡咯烷-1-基，或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基； R6为3-硝基苯胺基、3,4-二甲氧基苯甲氨基、3-碘苯甲氨基、吡啶-2-甲基氨基、吡啶-4-甲基氨基或茚-5-氨基； R9为异丙基或环戊基。 在另一个方面，本发明涉及包括所述化合物的制药组合物，以及在治疗抗增殖性疾病和/或病毒性疾病中使用它们的用途。

  公开号：

  US07612079B2

文献信息

• [EN] 2,6,9-SUBSTITUTED PURINE DERIVATIVES AND THEIR USE N THE TREATMENT OF PROLIFERATIVE DISORDERS<br/>[FR] DERIVES DE PURINE 2,6,9-SUBSTITUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES PROLIFERANTES
  申请人：CYCLACEL LTD

  公开号：WO2003002565A1

  公开（公告）日：2003-01-09

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R2 is 3-hydroxypiperidin-1-yl, or NHCH(R4)CH(R3) OH, wherein R3 is hydrogen or methyl and R4 is methyl, ethyl or isopropyl; R6 is 3-nitrophenylarnino, 3,4-dimethoxybenzylarnino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and/or viral disorders.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R2为3-羟基哌啶-1-基或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基；R6为3-硝基苯胺基、3,4-二甲氧基苄胺基、吡啶-2-基甲基氨基、吡啶-4-基甲基氨基或茚-5-基氨基；R9为异丙基或环戊基。在另一个方面，本发明涉及包含所述化合物的药物组合物，以及它们在治疗抗增殖性疾病和/或病毒性疾病中的应用。
• 2,6,9-Substituted purine derivatives and their use in the treatment of proliferative disorders
  申请人：Fischer Martin Peter

  公开号：US20050009846A1

  公开（公告）日：2005-01-13

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R 2 is 2-hydroxymethylpyrrolidin- 1 -yl, or NHCH(R 4 )CH(R 3 )OH, wherein R 3 is hydrogen or methyl and R 4 is methyl, ethyl or isopropyl; R 6 is 3-nitrophenylamino, 3,4-dimethoxybenzylamino, 3-iodobenzyl-amino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R 9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and or viral disorders.

  本发明涉及式I的化合物或其药学上可接受的盐，其中R2为2-羟甲基吡咯烷-1-基或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基；R6为3-硝基苯胺基、3,4-二甲氧基苯甲基氨基、3-碘苯甲基氨基、吡啶-2-基甲基氨基、吡啶-4-基甲基氨基或茚-5-基氨基；R9为异丙基或环戊基。在进一步方面，本发明涉及包括所述化合物的制药组合物及其在治疗抗增殖性疾病和/或病毒性疾病中的用途。
• 2,6,9-substituted purine derivatives and their use in the treatment of proliferative disorders
  申请人：Cyclacel Limited

  公开号：US07612079B2

  公开（公告）日：2009-11-03

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R2 is 2-hydroxymethylpyrrolidin-1-yl, or NHCH(R4)CH(R3)OH, wherein R3 is hydrogen or methyl and R4 is methyl, ethyl or isopropyl; R6 is 3-nitrophenylamino, 3,4-dimethoxybenzylamino, 3-iodobenzyl-amino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and or viral disorders.

  本发明涉及式I的化合物或其药学上可接受的盐，其中： R2为2-羟甲基吡咯烷-1-基，或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基； R6为3-硝基苯胺基、3,4-二甲氧基苯甲氨基、3-碘苯甲氨基、吡啶-2-甲基氨基、吡啶-4-甲基氨基或茚-5-氨基； R9为异丙基或环戊基。 在另一个方面，本发明涉及包括所述化合物的制药组合物，以及在治疗抗增殖性疾病和/或病毒性疾病中使用它们的用途。
• Discovery of novel purine derivatives with potent and selective inhibitory activity against c-Src tyrosine kinase
  作者：He Huang、Jingui Ma、Jianmei Shi、Linghua Meng、Hualiang Jiang、Jian Ding、Hong Liu

  DOI：10.1016/j.bmc.2010.05.032

  日期：2010.7

  We report here the discovery of novel purine derivatives with potent and selective inhibitory activity against c-Src tyrosine kinase by adopting a strategy integrating focused combinatorial library design, virtual screening, chemical synthesis, and bioassay. Thirty two compounds were selected and synthesized. All compounds showed potent inhibitory activity against c-Src kinase with IC50 values ranging from 3.14 mu M to 0.02 mu M. Compound 5i was identified as one of the most potent agent with an IC50 120 times lower than those of the hits. The high hit rate (100%) and the potency of the new Src kinase inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening. The novel active chemical entities reported here should be good leads for further development of purine-based anticancer drugs targeting Src tyrosine kinase. (C) 2010 Elsevier Ltd. All rights reserved.
• 2,6,9-SUBSTITUTED PURINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Cyclacel Limited

  公开号：EP1399446A1

  公开（公告）日：2004-03-24