phosphoric acid di-tert-butyl ester 1-(di-tert-butoxyphosphoryloxymethyl)-4-(6-methylamino-2-phenylpurin-9-yl)-bicyclo[3.1.0]hex-2-yl ester | 945565-64-0

• 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: phosphoric acid di-tert-butyl ester 1-(di-tert-butoxyphosphoryloxymethyl)-4-(6-methylamino-2-phenylpurin-9-yl)-bicyclo[3.1.0]hex-2-yl ester
• CAS: 945565-64-0
• 化学式: C₃₅H₅₅N₅O₈P₂
• 分子量: 735.798
• InChiKey: OBLLAMCPKUVDLJ-ZBRJBXLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.36
• 重原子数：
  50.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  145.15
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  phosphoric acid di-tert-butyl ester 1-(di-tert-butoxyphosphoryloxymethyl)-4-(6-methylamino-2-phenylpurin-9-yl)-bicyclo[3.1.0]hex-2-yl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 phosphoric acid mono-[4-(6-methylamino-2-phenylpurin-9-yl)-1-phosphonooxymethyl-bicyclo[3.1.0]hex-2-yl] ester
  参考文献：
  名称：

  P2Y₁ Antagonists:  Combining Receptor-Based Modeling and QSAR for a Quantitative Prediction of the Biological Activity Based on Consensus Scoring

  摘要：

  P2Y(1) is an ADP-activated G protein-coupled receptor (GPCR). Its antagonists impede platelet aggregation in vivo and are potential antithrombotic agents. Combining ligand and structure-based modeling we generated a consensus model (LIST-CM) correlating antagonist structures with their potencies. We docked 45 antagonists into our rhodopsin-based human P2Y(1) homology model and calculated docking scores and free binding energies with the Linear Interaction Energy (LIE) method in continuum-solvent. The resulting alignment was also used to build QSAR based on CoMFA, CoMSIA, and molecular descriptors. To benefit from the strength of each technique and compensate for their limitations, we generated our LIST-CM with a PLS regression based on the predictions of each methodology. A test set featuring untested substituents was synthesized and assayed in inhibition of 2-MeSADP-stimulated PLC activity and in radioligand binding. LIST-CM outperformed internal and external predictivity of any individual model to predict accurately the potency of 75% of the test set.

  DOI：

  10.1021/jm0700971
• 作为产物：
  描述：

  苯硼酸 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex sodium hydroxide 、 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 219.0h， 生成 phosphoric acid di-tert-butyl ester 1-(di-tert-butoxyphosphoryloxymethyl)-4-(6-methylamino-2-phenylpurin-9-yl)-bicyclo[3.1.0]hex-2-yl ester
  参考文献：
  名称：

  P2Y₁ Antagonists:  Combining Receptor-Based Modeling and QSAR for a Quantitative Prediction of the Biological Activity Based on Consensus Scoring

  摘要：

  P2Y(1) is an ADP-activated G protein-coupled receptor (GPCR). Its antagonists impede platelet aggregation in vivo and are potential antithrombotic agents. Combining ligand and structure-based modeling we generated a consensus model (LIST-CM) correlating antagonist structures with their potencies. We docked 45 antagonists into our rhodopsin-based human P2Y(1) homology model and calculated docking scores and free binding energies with the Linear Interaction Energy (LIE) method in continuum-solvent. The resulting alignment was also used to build QSAR based on CoMFA, CoMSIA, and molecular descriptors. To benefit from the strength of each technique and compensate for their limitations, we generated our LIST-CM with a PLS regression based on the predictions of each methodology. A test set featuring untested substituents was synthesized and assayed in inhibition of 2-MeSADP-stimulated PLC activity and in radioligand binding. LIST-CM outperformed internal and external predictivity of any individual model to predict accurately the potency of 75% of the test set.

  DOI：

  10.1021/jm0700971