1-Cyclohexyl-3-(2-furan-2-yl-8-octyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)-urea

• 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: 1-Cyclohexyl-3-(2-furan-2-yl-8-octyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)-urea
• 英文别名: 1-Cyclohexyl-3-[4-(furan-2-yl)-11-octyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea
• 化学式: C₂₅H₃₄N₈O₂
• 分子量: 478.597
• InChiKey: BAQIQAPZJHPHBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-呋喃甲酰肼 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 1-Cyclohexyl-3-(2-furan-2-yl-8-octyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)-urea
  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

• 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.