[(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]methyl-[[4-(2-hydroxyphenyl)phenyl]methyl]-dimethylazanium;iodide | 1413776-77-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]methyl-[[4-(2-hydroxyphenyl)phenyl]methyl]-dimethylazanium;iodide
• CAS: 1413776-77-8
• 化学式: C₂₅H₃₂NO*I
• 分子量: 489.44
• InChiKey: CTPIVYOGNWZNQS-IUQUCOCYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.63
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-(4-bromobenzyl)-1-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-N-methylmethanamine hydrochloride 、 2-羟基苯硼酸 在 sodium carbonate 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 121.58h， 生成 [(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]methyl-[[4-(2-hydroxyphenyl)phenyl]methyl]-dimethylazanium;iodide
  参考文献：
  名称：

  Chemical Subtleties in Small-Molecule Modulation of Peptide Receptor Function: The Case of CXCR3 Biaryl-Type Ligands

  摘要：

  The G protein-coupled chemokine receptor CXCR3 plays a role in numerous inflammatory events. The endogenous ligands for the chemokine receptors are peptides, but in this study we disclose small-molecule ligands that are able to activate CXCR3. A class of biaryl-type compounds that is assembled by convenient synthetic routes is described as a new class of CXCR3 agonists. Intriguingly, structure-activity relationship and structure-function relationship studies reveal that subtle chemical modifications on the outer aryl ring (e.g., either the size or position of a halogen atom) result in a full spectrum of agonist efficacies on CXCR3. Quantum mechanics calculations and nuclear Overhauser effect spectroscopy NMR studies suggest that the biaryl dihedral angle and the electronic nature of ortho-substituents play an important role in determining agonist efficacies. Compounds 38 (VUF11222) and 39 (VUF11418) are the first reported nonpeptidomimetic agonists on CXCR3, rendering them highly useful chemical tools for detailed assessment of CXCR3 activation as well as for studying downstream CXCR3 signaling.

  DOI：

  10.1021/jm301240t

文献信息

• Chemical Subtleties in Small-Molecule Modulation of Peptide Receptor Function: The Case of CXCR3 Biaryl-Type Ligands
  作者：Maikel Wijtmans、Danny J. Scholten、Luc Roumen、Meritxell Canals、Hans Custers、Marjolein Glas、Marlies C. A. Vreeker、Frans J. J. de Kanter、Chris de Graaf、Martine J. Smit、Iwan J. P. de Esch、Rob Leurs

  DOI：10.1021/jm301240t

  日期：2012.12.13

  The G protein-coupled chemokine receptor CXCR3 plays a role in numerous inflammatory events. The endogenous ligands for the chemokine receptors are peptides, but in this study we disclose small-molecule ligands that are able to activate CXCR3. A class of biaryl-type compounds that is assembled by convenient synthetic routes is described as a new class of CXCR3 agonists. Intriguingly, structure-activity relationship and structure-function relationship studies reveal that subtle chemical modifications on the outer aryl ring (e.g., either the size or position of a halogen atom) result in a full spectrum of agonist efficacies on CXCR3. Quantum mechanics calculations and nuclear Overhauser effect spectroscopy NMR studies suggest that the biaryl dihedral angle and the electronic nature of ortho-substituents play an important role in determining agonist efficacies. Compounds 38 (VUF11222) and 39 (VUF11418) are the first reported nonpeptidomimetic agonists on CXCR3, rendering them highly useful chemical tools for detailed assessment of CXCR3 activation as well as for studying downstream CXCR3 signaling.