adamantan-1-yl-(2-chloro-7(9)H-purin-6-yl)-amine | 39639-46-8

• 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: adamantan-1-yl-(2-chloro-7(9)H-purin-6-yl)-amine
• 英文别名: N-(1-adamantyl)-2-chloro-7H-purin-6-amine
• CAS: 39639-46-8
• 化学式: C₁₅H₁₈ClN₅
• 分子量: 303.794
• InChiKey: JMFYWUKEVMIUBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  adamantan-1-yl-(2-chloro-7(9)H-purin-6-yl)-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 6-(Adamantylamino)-2-[(3-hydroxypropyl)amino]-9-isopropylpurine
  参考文献：
  名称：

  Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase-2

  摘要：

  The cell division cycle is controlled by cyclin-dependent kinases (cdk), which consist of a catalytic subunit (cdk1-cdk8) and a regulatory subunit (cyclin A-H). Purine-like inhibitors of cyclin-dependent kinases have recently been found to be of potential use as anticancer drugs. Rigid and flexible docking techniques were used for analysis of binding mode and design of new inhibitors. X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. The new potential inhibitors were then docked into the cdk2 enzyme, and the enzyme/inhibitor interaction energies were calculated and tested against the assayed activities of cdk1 (37 compounds) and cdk2 (9 compounds). A significant rank correlation between the activity and the rigid docking interaction energy has been found. This implies that (i) the rigid docking can be used as a tool for qualitative prediction of activity and (ii) values obtained by the rigid docking technique into the cdk2 active site can also be used for the prediction of cdk1 activity. While the resulting geometries obtained by the rigid docking are in good agreement with the X-ray data, the flexible docking did not always produce the same inhibitor conformation as that found in the crystal.

  DOI：

  10.1021/jm990506w
• 作为产物：
  描述：

  金刚烷胺 、 2,6-二氯嘌呤 在 三乙胺 作用下， 以 正丁醇 为溶剂， 反应 3.0h， 生成 adamantan-1-yl-(2-chloro-7(9)H-purin-6-yl)-amine
  参考文献：
  名称：

  Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase-2

  摘要：

  The cell division cycle is controlled by cyclin-dependent kinases (cdk), which consist of a catalytic subunit (cdk1-cdk8) and a regulatory subunit (cyclin A-H). Purine-like inhibitors of cyclin-dependent kinases have recently been found to be of potential use as anticancer drugs. Rigid and flexible docking techniques were used for analysis of binding mode and design of new inhibitors. X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. The new potential inhibitors were then docked into the cdk2 enzyme, and the enzyme/inhibitor interaction energies were calculated and tested against the assayed activities of cdk1 (37 compounds) and cdk2 (9 compounds). A significant rank correlation between the activity and the rigid docking interaction energy has been found. This implies that (i) the rigid docking can be used as a tool for qualitative prediction of activity and (ii) values obtained by the rigid docking technique into the cdk2 active site can also be used for the prediction of cdk1 activity. While the resulting geometries obtained by the rigid docking are in good agreement with the X-ray data, the flexible docking did not always produce the same inhibitor conformation as that found in the crystal.

  DOI：

  10.1021/jm990506w

文献信息

• Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase-2
  作者：Michal Otyepka、Vladimír Kryštof、Libor Havlíček、Věra Siglerová、Miroslav Strnad、Jaroslav Koča

  DOI：10.1021/jm990506w

  日期：2000.6.1

  The cell division cycle is controlled by cyclin-dependent kinases (cdk), which consist of a catalytic subunit (cdk1-cdk8) and a regulatory subunit (cyclin A-H). Purine-like inhibitors of cyclin-dependent kinases have recently been found to be of potential use as anticancer drugs. Rigid and flexible docking techniques were used for analysis of binding mode and design of new inhibitors. X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. The new potential inhibitors were then docked into the cdk2 enzyme, and the enzyme/inhibitor interaction energies were calculated and tested against the assayed activities of cdk1 (37 compounds) and cdk2 (9 compounds). A significant rank correlation between the activity and the rigid docking interaction energy has been found. This implies that (i) the rigid docking can be used as a tool for qualitative prediction of activity and (ii) values obtained by the rigid docking technique into the cdk2 active site can also be used for the prediction of cdk1 activity. While the resulting geometries obtained by the rigid docking are in good agreement with the X-ray data, the flexible docking did not always produce the same inhibitor conformation as that found in the crystal.