11-(Cyclohexylmethyl)-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine | 827629-35-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 11-(Cyclohexylmethyl)-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine
• CAS: 827629-35-6
• 化学式: C₁₇H₁₉N₇O
• 分子量: 337.384
• InChiKey: LCCFLWNPZZEHAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4-异氰酰基苯基)乙酸乙酯 、 11-(Cyclohexylmethyl)-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以69%的产率得到Ethyl 2-[4-[[11-(cyclohexylmethyl)-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]carbamoylamino]phenyl]acetate
  参考文献：
  名称：

  Combined Target-Based and Ligand-Based Drug Design Approach as a Tool To Define a Novel 3D-Pharmacophore Model of Human A₃ Adenosine Receptor Antagonists:  Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine Derivatives as a Key Study

  摘要：

  A combined target-based and ligand-based drug design approach has been carried out to define a novel pharmacophore model of the human A(3) receptor antagonists. High throughput molecular docking and comparative molecular field analysis (CoMFA) have been used in tandem to assemble a new target based pharmacophore model. In parallel, to provide more accurate information about the putative binding site of these A(3) inhibitors, a rhodopsin-based model of the human A(3) receptor was built and a novel Y-shape binding motif has been proposed. Docking-based structure superimposition has been used to perform a quantitative study of the structure-activity relationships for binding of these pyrazolo-triazolo-pyrimidines to adenosine A(3) receptor using CoMFA. Both steric and the electrostatic contour plots obtained from the CoMFA analysis nicely fit on the hypothetical binding site obtained by molecular docking. On the basis of the combined hypothesis, we have designed, synthesized, and tested 17 new derivatives. Consistently, the predicted K-i values were very close to the experimental values.

  DOI：

  10.1021/jm049662f
• 作为产物：
  描述：

  2-呋喃甲酰肼 、 氰胺 、 3-氨基-4-氰基吡唑 、 alkaline earth salt of/the/ methylsulfuric acid 以38%的产率得到11-(Cyclohexylmethyl)-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine
  参考文献：
  名称：

  Combined Target-Based and Ligand-Based Drug Design Approach as a Tool To Define a Novel 3D-Pharmacophore Model of Human A₃ Adenosine Receptor Antagonists:  Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine Derivatives as a Key Study

  摘要：

  A combined target-based and ligand-based drug design approach has been carried out to define a novel pharmacophore model of the human A(3) receptor antagonists. High throughput molecular docking and comparative molecular field analysis (CoMFA) have been used in tandem to assemble a new target based pharmacophore model. In parallel, to provide more accurate information about the putative binding site of these A(3) inhibitors, a rhodopsin-based model of the human A(3) receptor was built and a novel Y-shape binding motif has been proposed. Docking-based structure superimposition has been used to perform a quantitative study of the structure-activity relationships for binding of these pyrazolo-triazolo-pyrimidines to adenosine A(3) receptor using CoMFA. Both steric and the electrostatic contour plots obtained from the CoMFA analysis nicely fit on the hypothetical binding site obtained by molecular docking. On the basis of the combined hypothesis, we have designed, synthesized, and tested 17 new derivatives. Consistently, the predicted K-i values were very close to the experimental values.

  DOI：

  10.1021/jm049662f

文献信息

• The application of a 3D-QSAR (autoMEP/PLS) approach as an efficient pharmacodynamic-driven filtering method for small-sized virtual library: Application to a lead optimization of a human A3 adenosine receptor antagonist
  作者：Stefano Moro、Magdalena Bacilieri、Barbara Cacciari、Chiara Bolcato、Claudia Cusan、Giorgia Pastorin、Karl-Norbert Klotz、Giampiero Spalluto

  DOI：10.1016/j.bmc.2006.03.010

  日期：2006.7.15

  We have recently reported that the combination of molecular electrostatic potential (MEP) surface properties (autocorrelation vectors) with the conventional partial least squares (PLS) analysis can be used to produce a robust ligand-based 3D structure-activity relationship (autoMEP/PLS) for the prediction of the human A(3) receptor antagonist activities. Here, we present the application of the 3D-QSAR (autoMEP/PLS) approach as an efficient and alternative pharmacodynamic filtering method for small-sized virtual library. For this purpose, a small-sized combinatorial library (841 compounds) was derived from the scaffold of the known human A(3) antagonist pyrazolo-triazolo-pyrimidines. The most interesting analogues were further prioritized for synthesis and pharmacological characterization. Remarkably, we have found that all the newly synthetized compounds are correctly predicted as potent human A(3) antagonists, In particular, two of them are correctly predicted as sub-nanomolar inhibitors of the human A3 receptor. (c) 2006 Elsevier Ltd. All rights reserved.
• Combined Target-Based and Ligand-Based Drug Design Approach as a Tool To Define a Novel 3D-Pharmacophore Model of Human A₃ Adenosine Receptor Antagonists:  Pyrazolo[4,3-<i>e</i>]1,2,4-triazolo[1,5-<i>c</i>]pyrimidine Derivatives as a Key Study
  作者：Stefano Moro、Paolo Braiuca、Francesca Deflorian、Cristina Ferrari、Giorgia Pastorin、Barbara Cacciari、Pier Giovanni Baraldi、Katia Varani、Pier Andrea Borea、Giampiero Spalluto

  DOI：10.1021/jm049662f

  日期：2005.1.1

  A combined target-based and ligand-based drug design approach has been carried out to define a novel pharmacophore model of the human A(3) receptor antagonists. High throughput molecular docking and comparative molecular field analysis (CoMFA) have been used in tandem to assemble a new target based pharmacophore model. In parallel, to provide more accurate information about the putative binding site of these A(3) inhibitors, a rhodopsin-based model of the human A(3) receptor was built and a novel Y-shape binding motif has been proposed. Docking-based structure superimposition has been used to perform a quantitative study of the structure-activity relationships for binding of these pyrazolo-triazolo-pyrimidines to adenosine A(3) receptor using CoMFA. Both steric and the electrostatic contour plots obtained from the CoMFA analysis nicely fit on the hypothetical binding site obtained by molecular docking. On the basis of the combined hypothesis, we have designed, synthesized, and tested 17 new derivatives. Consistently, the predicted K-i values were very close to the experimental values.