1-[8-(2-Benzyloxy-ethyl)-2-furan-2-yl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-3-pyridin-4-yl-urea | 897025-54-6

• 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: 1-[8-(2-Benzyloxy-ethyl)-2-furan-2-yl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-3-pyridin-4-yl-urea
• 英文别名: 1-[4-(Furan-2-yl)-11-(2-phenylmethoxyethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-pyridin-4-ylurea
• CAS: 897025-54-6
• 化学式: C₂₅H₂₁N₉O₃
• 分子量: 495.5
• InChiKey: KEOFEPBQPNRHDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-[8-(2-Benzyloxy-ethyl)-2-furan-2-yl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-3-pyridin-4-yl-urea 在 palladium on activated charcoal 、 甲酸铵 作用下， 以 丙酮 为溶剂， 反应 12.0h， 生成 1-[2-Furan-2-yl-8-(2-hydroxy-ethyl)-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-3-pyridin-4-yl-urea
  参考文献：
  名称：

  Pharmacophore Based Receptor Modeling:  The Case of Adenosine A₃ Receptor Antagonists. An Approach to the Optimization of Protein Models

  摘要：

  To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecular model of the receptor built by homology modeling. The alignment of the ligands proposed by Catalyst was then used to manually dock a set of known A(3) antagonists into the binding site, and as a result, the model was able to explain the different binding mode of very active compounds with respect to less active ones and to reproduce, with good accuracy, free energies of binding. The docking highlighted that the nonconserved residue Tyr254 could play an important role for A(3) selectivity, suggesting that a mutagenesis study on this residue could be of interest in this respect. The reliability of the whole approach was successfully tested by rational design and synthesis of new compounds.

  DOI：

  10.1021/jm051112+
• 作为产物：
  描述：

  2-(5-Amino-2-furan-2-yl-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-8-yl)-ethanol 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 1-[8-(2-Benzyloxy-ethyl)-2-furan-2-yl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-3-pyridin-4-yl-urea
  参考文献：
  名称：

  Pharmacophore Based Receptor Modeling:  The Case of Adenosine A₃ Receptor Antagonists. An Approach to the Optimization of Protein Models

  摘要：

  To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecular model of the receptor built by homology modeling. The alignment of the ligands proposed by Catalyst was then used to manually dock a set of known A(3) antagonists into the binding site, and as a result, the model was able to explain the different binding mode of very active compounds with respect to less active ones and to reproduce, with good accuracy, free energies of binding. The docking highlighted that the nonconserved residue Tyr254 could play an important role for A(3) selectivity, suggesting that a mutagenesis study on this residue could be of interest in this respect. The reliability of the whole approach was successfully tested by rational design and synthesis of new compounds.

  DOI：

  10.1021/jm051112+

文献信息

• Pharmacophore Based Receptor Modeling:  The Case of Adenosine A₃ Receptor Antagonists. An Approach to the Optimization of Protein Models
  作者：Andrea Tafi、Cesare Bernardini、Maurizio Botta、Federico Corelli、Matteo Andreini、Adriano Martinelli、Gabriella Ortore、Pier Giovanni Baraldi、Francesca Fruttarolo、Pier Andrea Borea、Tiziano Tuccinardi

  DOI：10.1021/jm051112+

  日期：2006.7.1

  To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecular model of the receptor built by homology modeling. The alignment of the ligands proposed by Catalyst was then used to manually dock a set of known A(3) antagonists into the binding site, and as a result, the model was able to explain the different binding mode of very active compounds with respect to less active ones and to reproduce, with good accuracy, free energies of binding. The docking highlighted that the nonconserved residue Tyr254 could play an important role for A(3) selectivity, suggesting that a mutagenesis study on this residue could be of interest in this respect. The reliability of the whole approach was successfully tested by rational design and synthesis of new compounds.