9-(2-hydroxyethyl)-2-(3-methoxybenzyl)-1,9-dihydropurin-6-one | 1227069-11-5

• 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: 9-(2-hydroxyethyl)-2-(3-methoxybenzyl)-1,9-dihydropurin-6-one
• 英文别名: 9-(2-hydroxyethyl)-2-[(3-methoxyphenyl)methyl]-1H-purin-6-one
• CAS: 1227069-11-5
• 化学式: C₁₅H₁₆N₄O₃
• 分子量: 300.317
• InChiKey: WZLVKLWOOMCHBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  88.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-甲氧基苯乙酸甲酯 、 5-amino-1-(2-hydroxyethyl)imidazole-4-carboxamide 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 9-(2-hydroxyethyl)-2-(3-methoxybenzyl)-1,9-dihydropurin-6-one
  参考文献：
  名称：

  Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors

  摘要：

  合成了一系列嘌呤-6-酮衍生物，并利用荧光极化测定法评估它们对磷酸二酯酶-2（PDE2）的体外抑制活性。其中三种化合物，即2j、2p和2q，显示出对PDE2的显著抑制活性，其IC50值分别为1.73、0.18和3.43 μM。进行了结构活性关系（SAR）分析，以探索这些化合物的化学结构与它们的抑制活性之间的关系。化合物2j、2p和2q进一步被选择用于分子对接研究。对接结果表明，这些配体与PDE2的催化活性位点的疏水口袋结合，其中Tyr655残基被发现在与化合物2p结合中起重要作用，这是本研究中发现的最有效的抑制剂。我们的研究为未来设计新型PDE2抑制剂提供了有用的信息。

  DOI：

  10.1155/2016/6878353

文献信息

• Structural Assignment of 6-Oxy Purine Derivatives through Computational Modeling, Synthesis, X-ray Diffraction, and Spectroscopic Analysis
  作者：Xinyun Zhao、Xi Chen、Guang-Fu Yang、Chang-Guo Zhan

  DOI：10.1021/jp100039p

  日期：2010.5.27

  6-Oxy purine derivatives have been considered as potential therapeutic agents in various drug discovery efforts reported in the literature. However, the structural assignment of this important class of compounds has been controversial concerning the specific position of a hydrogen atom in the structure. To theoretically determine the most favorable type of tautomeric form of 6-oxy purine derivatives, we have carried out first-principles electronic structure calculations on the possible tautomeric forms (A, B, and C) and their relative stability of four representative 6-oxy purine derivatives (compounds 1-4). The computational results in both the gas phase and aqueous solution clearly reveal that the most favorable type of tautomeric form of these compounds is A, in which a hydrogen atom bonds with the NI atom on the purine ring. To examine the computational results, one of the 6-oxy purine derivatives (i.e., compound 4) has been synthesized and its structure has been characterized by X-ray diffraction and spectroscopic analysis. All of the obtained computational and experimental data are consistent with the conclusion that the 6-oxy purine derivative exists in tautomer A. The conclusive structural assignment reported here is expected to be valuable for future computational studies on 6-oxy purine derivative binding with proteins and for computational drug design involving this type of compounds.
• Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors
  作者：Wei Yuan、Xin-Yun Zhao、Xi Chen、Chang-Guo Zhan

  DOI：10.1155/2016/6878353

  日期：——

  A series of purin-6-one derivatives were synthesized, and theirin vitroinhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are,2j,2p, and2q, showed significant inhibitory activity against PDE2 with IC₅₀values of 1.73, 0.18, and 3.43 μM, respectively. Structure-activity relationship (SAR) analysis was performed to explore the relationship between the chemical structures of these compounds and their inhibitory activity. Compounds2j,2p, and2qwere further selected for molecular docking study. The docking results suggested that these ligands bind with hydrophobic pockets of the catalytic active site of PDE2, where a Tyr655 residue was found to be important in binding with compound2p, the most potent inhibitor identified in this study. Our present study provides useful information for the future design of novel PDE2 inhibitors.

  合成了一系列嘌呤-6-酮衍生物，并利用荧光极化测定法评估它们对磷酸二酯酶-2（PDE2）的体外抑制活性。其中三种化合物，即2j、2p和2q，显示出对PDE2的显著抑制活性，其IC50值分别为1.73、0.18和3.43 μM。进行了结构活性关系（SAR）分析，以探索这些化合物的化学结构与它们的抑制活性之间的关系。化合物2j、2p和2q进一步被选择用于分子对接研究。对接结果表明，这些配体与PDE2的催化活性位点的疏水口袋结合，其中Tyr655残基被发现在与化合物2p结合中起重要作用，这是本研究中发现的最有效的抑制剂。我们的研究为未来设计新型PDE2抑制剂提供了有用的信息。