N-(4-bromobenzyl)-1-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-N-methylmethanamine | 1313884-67-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-(4-bromobenzyl)-1-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-N-methylmethanamine
• 英文别名: N-[(4-bromophenyl)methyl]-1-[(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]-N-methylmethanamine
• CAS: 1313884-67-1
• 化学式: C₁₈H₂₄BrN
• 分子量: 334.299
• InChiKey: BGMZTQKGOMILFX-RDJZCZTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(4-bromobenzyl)-1-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-N-methylmethanamine 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 反应 1.5h， 生成 [(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]methyl-[[4-(2-fluorophenyl)phenyl]methyl]-dimethylazanium;iodide
  参考文献：
  名称：

  CXCR3 antagonists: Quaternary ammonium salts equipped with biphenyl- and polycycloaliphatic-anchors

  摘要：

  Small-molecule ligands for the CXCR3 chemokine receptor receive considerable attention as a means to interrogate the roles of CXCR3 in vitro and in vivo and/or to potentially treat various conditions such as inflammatory diseases and cancer. We have synthesized and explored a novel class of small-molecule antagonists for CXCR3. A medium-throughput screen revealed an adamantane-guanidine as a hit. The guanidine unit was replaced by a small quaternary ammonium group, leading to ca. 5-fold increase in affinity. Substitution of the adamantane group by a myrtenyl moiety further increased affinity, while the benzyl group was decorated with an additional (substituted) aryl ring. This led to the identification of several bisaryl-based ligands with CXCR3 affinities of around 100 nM and with the ability to antagonize the functional activity of CXCL10. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.035
• 作为产物：
  描述：

  桃金娘烯醛 在 甲酸 、 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 水 、 1,2-二氯乙烷 为溶剂， 反应 48.17h， 生成 N-(4-bromobenzyl)-1-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-N-methylmethanamine
  参考文献：
  名称：

  CXCR3 antagonists: Quaternary ammonium salts equipped with biphenyl- and polycycloaliphatic-anchors

  摘要：

  Small-molecule ligands for the CXCR3 chemokine receptor receive considerable attention as a means to interrogate the roles of CXCR3 in vitro and in vivo and/or to potentially treat various conditions such as inflammatory diseases and cancer. We have synthesized and explored a novel class of small-molecule antagonists for CXCR3. A medium-throughput screen revealed an adamantane-guanidine as a hit. The guanidine unit was replaced by a small quaternary ammonium group, leading to ca. 5-fold increase in affinity. Substitution of the adamantane group by a myrtenyl moiety further increased affinity, while the benzyl group was decorated with an additional (substituted) aryl ring. This led to the identification of several bisaryl-based ligands with CXCR3 affinities of around 100 nM and with the ability to antagonize the functional activity of CXCL10. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.035

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.
• CXCR3 antagonists: Quaternary ammonium salts equipped with biphenyl- and polycycloaliphatic-anchors
  作者：Maikel Wijtmans、Dennis Verzijl、Serge Bergmans、Michael Lai、Leontien Bosch、Martine J. Smit、Iwan J.P. de Esch、Rob Leurs

  DOI：10.1016/j.bmc.2011.04.035

  日期：2011.6

  Small-molecule ligands for the CXCR3 chemokine receptor receive considerable attention as a means to interrogate the roles of CXCR3 in vitro and in vivo and/or to potentially treat various conditions such as inflammatory diseases and cancer. We have synthesized and explored a novel class of small-molecule antagonists for CXCR3. A medium-throughput screen revealed an adamantane-guanidine as a hit. The guanidine unit was replaced by a small quaternary ammonium group, leading to ca. 5-fold increase in affinity. Substitution of the adamantane group by a myrtenyl moiety further increased affinity, while the benzyl group was decorated with an additional (substituted) aryl ring. This led to the identification of several bisaryl-based ligands with CXCR3 affinities of around 100 nM and with the ability to antagonize the functional activity of CXCL10. (C) 2011 Elsevier Ltd. All rights reserved.