2,6-dichloropurinyl-9-(1-ethoxytetrahydropyran) | 186692-48-8

• 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: 2,6-dichloropurinyl-9-(1-ethoxytetrahydropyran)
• 英文别名: 2,6-Dichloro-9-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-9H-purine；2,6-Dichloro-9-[2-(oxan-2-yloxy)ethyl]purine
• CAS: 186692-48-8
• 化学式: C₁₂H₁₄Cl₂N₄O₂
• 分子量: 317.175
• InChiKey: GGAKJRVWPIIXOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  62.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-dichloropurinyl-9-(1-ethoxytetrahydropyran) 在 三乙胺 作用下， 以 正丁醇 为溶剂， 反应 5.0h， 生成 2-{6-Benzylamino-9-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-9H-purin-2-ylamino}-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：

  3,4-二氢-2H-吡喃 在 Amberlyst 15 、 sodium hydride 作用下， 反应 5.0h， 生成 2,6-dichloropurinyl-9-(1-ethoxytetrahydropyran)
  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

文献信息

• Synthesis of Boron-Containing Nucleoside Analogs
  作者：Latifah M. Alhthlol、Christopher L. Orme、Ben S. Jefferis、Sarah A. Herter、Halee E. Kemper、John W. Tomsho

  DOI：10.1021/acs.joc.3c02179

  日期：2024.2.2

  boron-containing nucleoside compound libraries which may find utility as therapeutic agents. Our synthetic strategy employs efficient one-step substitution reactions between a diverse variety of nucleoside scaffolds and an assortment of n-alkyl potassium trifluoroborate-containing electrophiles. We demonstrated that these alkylation reactions are compatible with cyclic and acyclic nucleoside substrates,

  在上个世纪，基于核苷的疗法在治疗从癌症到艾滋病毒等多种疾病方面表现出了显着的有效性。此外，含硼药物最近已成为一种令人兴奋且富有成效的药物治疗途径。然而，硼核苷在医学应用方面很大程度上尚未得到探索。在此，我们报告了两种新型含硼核苷化合物库的合成、分离和表征，它们可能用作治疗剂。我们的合成策略采用多种核苷支架和各种含正烷基三氟硼酸钾的亲电子试剂之间的高效一步取代反应。我们证明这些烷基化反应与环状和无环核苷底物以及增加的烷基链长度兼容。此外，通过控制碱基特性和反应温度条件可以容易地实现产物形成的区域选择性控制。