2-chloro-N-(cyclohexylmethyl)-9H-purine-6-amine | 1026726-88-4

• 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-N-(cyclohexylmethyl)-9H-purine-6-amine
• 英文别名: 2-chloro-N-(cyclohexylmethyl)-7H-purin-6-amine
• CAS: 1026726-88-4
• 化学式: C₁₂H₁₆ClN₅
• 分子量: 265.746
• InChiKey: TWIUFJSTJRNQMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(cyclohexylmethyl)-9H-purine-6-amine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-[[6-(Cyclohexylmethylamino)-9-methylpurin-2-yl]amino]ethanol
  参考文献：
  名称：

  Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors:  Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

  摘要：

  Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3, and 7 positions of the purine ring must remain free, probably for a direct interaction, in which it behaves as a hydrogen bond acceptor. Olomoucine (6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-methylpurine, OC), roscovitine (6-(benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine), and other N-6,2,9-trisubstituted adenines were found to exert a strong inhibitory effect on the p34(cdc2)/cyclin B kinase. Removal or change of the side chain at position 2 or the hydrophobic group at position 9 dramatically decreased the inhibitory activity of olomoucine or roscovitine. Inhibition of cdk with OC and related compounds clearly arrests cell proliferation of many tumor cell lines at G(1)/S and G(2)/M transitions and also triggers apoptosis in the target tumor cells in vitro and in vivo. Thus, from a pharmacological point of view, OC may represent a model compound for a new class of antimitotic and antitumor drugs.

  DOI：

  10.1021/jm960666x
• 作为产物：
  描述：

  2,6-二氯嘌呤 、 环己甲胺 在 三氟乙酸 作用下， 以 正丁醇 为溶剂， 反应 5.0h， 以91%的产率得到2-chloro-N-(cyclohexylmethyl)-9H-purine-6-amine
  参考文献：
  名称：

  嘌呤-2,6-二胺衍生物作为细胞周期蛋白依赖性激酶（CDK）抑制剂的设计，合成和初步生物学评估

  摘要：

  设计并合成了新型嘌呤-2,6-二胺衍生物，作为细胞周期蛋白依赖性激酶（CDK）抑制剂。根据初步的生物学评估，大多数化合物在CDK1酶分析中显示出良好的抑制活性，并且在某些肿瘤细胞系中显示出强大的抗增殖活性。尤其是，化合物11a（CDK1 /细胞周期蛋白B的IC 50 = 0.35 µmol / L，CDK2 /细胞周期蛋白A的IC 50 = 0.023 µmol / L）与Roscovitine（IC 50 = 2.54（CDK1 /细胞周期蛋白B和CD 50 /细胞周期蛋白A的IC 50 = 0.092 µmol / L）。

  DOI：

  10.1002/cjoc.201300420

文献信息

• Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors:  Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds
  作者：Libor Havlíček、Jan Hanuš、Jaroslav Veselý、Sophie Leclerc、Laurent Meijer、Gordon Shaw、Miroslav Strnad

  DOI：10.1021/jm960666x

  日期：1997.2.1

  Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3, and 7 positions of the purine ring must remain free, probably for a direct interaction, in which it behaves as a hydrogen bond acceptor. Olomoucine (6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-methylpurine, OC), roscovitine (6-(benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine), and other N-6,2,9-trisubstituted adenines were found to exert a strong inhibitory effect on the p34(cdc2)/cyclin B kinase. Removal or change of the side chain at position 2 or the hydrophobic group at position 9 dramatically decreased the inhibitory activity of olomoucine or roscovitine. Inhibition of cdk with OC and related compounds clearly arrests cell proliferation of many tumor cell lines at G(1)/S and G(2)/M transitions and also triggers apoptosis in the target tumor cells in vitro and in vivo. Thus, from a pharmacological point of view, OC may represent a model compound for a new class of antimitotic and antitumor drugs.
• Design, Synthesis and Preliminary Biological Evaluation of Purine-2,6-diamine Derivatives as Cyclin-dependent Kinase (CDK) Inhibitors
  作者：Junhua Wang、Quande Wang、Liangren Zhang、Hao Fang

  DOI：10.1002/cjoc.201300420

  日期：2013.9

  Novel purine‐2,6‐diamine derivatives were designed and synthesized as cyclin‐dependent kinase (CDK) inhibitors. According to the preliminary biological evaluation, most of the compounds show good inhibitory activities in CDK1 enzyme assay and potent antiproliferative activities in some tumor cell lines. Especially, compound 11a (IC50=0.35 µmol/L for CDK1/cyclin B and IC50=0.023 µmol/L for CDK2/cyclin

  设计并合成了新型嘌呤-2,6-二胺衍生物，作为细胞周期蛋白依赖性激酶（CDK）抑制剂。根据初步的生物学评估，大多数化合物在CDK1酶分析中显示出良好的抑制活性，并且在某些肿瘤细胞系中显示出强大的抗增殖活性。尤其是，化合物11a（CDK1 /细胞周期蛋白B的IC 50 = 0.35 µmol / L，CDK2 /细胞周期蛋白A的IC 50 = 0.023 µmol / L）与Roscovitine（IC 50 = 2.54（CDK1 /细胞周期蛋白B和CD 50 /细胞周期蛋白A的IC 50 = 0.092 µmol / L）。