4-(2-triisopropylsiloxyethyl)-1-bromonaphthalene | 865360-06-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(2-triisopropylsiloxyethyl)-1-bromonaphthalene
• 英文别名: 2-(4-Bromonaphthalen-1-yl)ethoxy-tri(propan-2-yl)silane
• CAS: 865360-06-1
• 化学式: C₂₁H₃₁BrOSi
• 分子量: 407.466
• InChiKey: CFMKULQSSXSDEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.34
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-(2-triisopropylsiloxyethyl)-1-bromonaphthalene 在 正丁基锂 、 草酰氯 、 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 3-(4-(2-triisopropylsiloxyethyl)naphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography

  摘要：

  A new series of CB1 ligands with high binding affinity (K-i = 0.7-100 nM) and moderate lipophilicity (cLogD(7.4)) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with F-18. This radioligand specifically labeled CB, receptors in mouse brain and accumulated in regions of high versus low CB1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB, antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the racemate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.

  DOI：

  10.1021/jm0502743
• 作为产物：
  描述：

  三异丙基氯硅烷 、 2-(4-bromonaphthalen-1-yl)ethan-1-ol 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以99%的产率得到4-(2-triisopropylsiloxyethyl)-1-bromonaphthalene
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography

  摘要：

  A new series of CB1 ligands with high binding affinity (K-i = 0.7-100 nM) and moderate lipophilicity (cLogD(7.4)) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with F-18. This radioligand specifically labeled CB, receptors in mouse brain and accumulated in regions of high versus low CB1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB, antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the racemate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.

  DOI：

  10.1021/jm0502743

文献信息

• Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography
  作者：Peter G. Willis、Olga A. Pavlova、Svetlana I. Chefer、D. Bruce Vaupel、Alexey G. Mukhin、Andrew G. Horti

  DOI：10.1021/jm0502743

  日期：2005.9.1

  A new series of CB1 ligands with high binding affinity (K-i = 0.7-100 nM) and moderate lipophilicity (cLogD(7.4)) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with F-18. This radioligand specifically labeled CB, receptors in mouse brain and accumulated in regions of high versus low CB1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB, antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the racemate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.