tert-butyl (3-exo)-8-azabicyclo[3.2.1]oct-3-ylcarbamate hydrochloride | 530135-00-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: tert-butyl (3-exo)-8-azabicyclo[3.2.1]oct-3-ylcarbamate hydrochloride
• CAS: 530135-00-3
• 化学式: C₁₂H₂₂N₂O₂*ClH
• 分子量: 262.78
• InChiKey: FAJOKGXZZTZLAU-ISZLRMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  50.36
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (3-exo)-8-azabicyclo[3.2.1]oct-3-ylcarbamate hydrochloride 、 2-bromomethyl-6-fluoronaphthalene 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 以100%的产率得到tert-butyl {(3-exo)-8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}carbamate
  参考文献：
  名称：

  Design and synthesis of 6-fluoro-2-naphthyl derivatives as novel CCR3 antagonists with reduced CYP2D6 inhibition

  摘要：

  In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC(50) value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC(50) value of 400 nM. In order to reduce its CYP2D6 inhibitory activity, we performed further systematic structural modi. cations on 1. In particular, we focused on reducing the number of lipophilic moieties in the biphenyl part of 1, using Clog D(7.4) values as the reference index of lipophilicity. This research led to the identification of N-{(3-exo)-8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-3-(piperidin-1-ylcarbonyl)isonicotinamide 1-oxide (30) which showed comparable CCR3 inhibitory activity (IC(50) = 23 nM) with much reduced CYP2D6 inhibitory activity (IC50 = 29,000 nM) compared with 1. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.006
• 作为产物：
  描述：

  tert-butyl (3-exo-8-benzyl-8-azabicyclo[3.2.1]oct-3-yl)carbamate 在 palladium dihydroxide 盐酸 、 氢气 作用下， 以 甲醇 、 乙醇 、 乙酸乙酯 为溶剂， 反应 3.0h， 以96%的产率得到tert-butyl (3-exo)-8-azabicyclo[3.2.1]oct-3-ylcarbamate hydrochloride
  参考文献：
  名称：

  Design and synthesis of 6-fluoro-2-naphthyl derivatives as novel CCR3 antagonists with reduced CYP2D6 inhibition

  摘要：

  In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC(50) value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC(50) value of 400 nM. In order to reduce its CYP2D6 inhibitory activity, we performed further systematic structural modi. cations on 1. In particular, we focused on reducing the number of lipophilic moieties in the biphenyl part of 1, using Clog D(7.4) values as the reference index of lipophilicity. This research led to the identification of N-{(3-exo)-8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-3-(piperidin-1-ylcarbonyl)isonicotinamide 1-oxide (30) which showed comparable CCR3 inhibitory activity (IC(50) = 23 nM) with much reduced CYP2D6 inhibitory activity (IC50 = 29,000 nM) compared with 1. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.006