2-[4-(Benzyloxy)-1-naphthyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[4-(Benzyloxy)-1-naphthyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• 英文别名: 4,4,5,5-tetramethyl-2-(4-phenylmethoxynaphthalen-1-yl)-1,3,2-dioxaborolane
• 化学式: C₂₃H₂₅BO₃
• mdl: MFCD28505152
• 分子量: 360.261
• InChiKey: BKBHQKNQVGZWLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.72
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  、 2-[4-(Benzyloxy)-1-naphthyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium fluoride 作用下， 以 甲醇 为溶剂， 反应 0.17h， 以46%的产率得到
  参考文献：
  名称：

  Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy

  摘要：

  Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (alpha-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood -brain barrier permeability in nonhuman primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate alpha-syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analogue 14, were then radiolabeled with C-11 (t(1/2) = 20.4 min) at high radiochemical purity (>99%) and high specific radioactivity (>37 GBq/mu mol). Following intravenous injection of each compound in NHP, a 4-fold higher radioactivity in brain was observed for [C-11]14 compared to [C-11]12 (0.8 vs 0.2 SUV, respectively). [C-11]14 was rapidly eliminated from plasma, with [C-11]12 as the major metabolic product observed by radio-HPLC. The presented prodrug approach paves the way for future development of 2-pyridones as imaging biomarkers for in vivo imaging of alpha-synuclein deposits in brain.

  DOI：

  10.1021/acschemneuro.8b00236
• 作为产物：
  描述：

  1-溴-4-苯基甲氧基萘 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 以86%的产率得到2-[4-(Benzyloxy)-1-naphthyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
  参考文献：
  名称：

  Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy

  摘要：

  Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (alpha-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood -brain barrier permeability in nonhuman primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate alpha-syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analogue 14, were then radiolabeled with C-11 (t(1/2) = 20.4 min) at high radiochemical purity (>99%) and high specific radioactivity (>37 GBq/mu mol). Following intravenous injection of each compound in NHP, a 4-fold higher radioactivity in brain was observed for [C-11]14 compared to [C-11]12 (0.8 vs 0.2 SUV, respectively). [C-11]14 was rapidly eliminated from plasma, with [C-11]12 as the major metabolic product observed by radio-HPLC. The presented prodrug approach paves the way for future development of 2-pyridones as imaging biomarkers for in vivo imaging of alpha-synuclein deposits in brain.

  DOI：

  10.1021/acschemneuro.8b00236