1-((1R,2R,3S,5S)-8-(2-chloroethyl)-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]octan-2-yl)-N,N-dimethylmethanamine | 1384179-29-6

• 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: 1-((1R,2R,3S,5S)-8-(2-chloroethyl)-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]octan-2-yl)-N,N-dimethylmethanamine
• CAS: 1384179-29-6
• 化学式: C₁₈H₂₆Cl₂N₂
• 分子量: 341.324
• InChiKey: MHBSAOIASLLEIS-XWTMOSNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  6.48
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-((1R,2R,3S,5S)-8-(2-chloroethyl)-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]octan-2-yl)-N,N-dimethylmethanamine 在 [18F]fluoride ion 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二甲基亚砜 为溶剂， 反应 0.17h， 生成 1-[(1R,2R,3S,5S)-3-(4-chlorophenyl)-8-(2-(18F)fluoranylethyl)-8-azabicyclo[3.2.1]octan-2-yl]-N,N-dimethylmethanamine
  参考文献：
  名称：

  Synthesis and evaluation of novel tropane derivatives as potential PET imaging agents for the dopamine transporter

  摘要：

  A novel series of tropane derivatives containing a fluorinated tertiary amino or amide at the 2 beta position was synthesized, labeled with the positron-emitter fluorine-18 (t(1/2) = 109.8 min), and tested as potential in vivo dopamine transporter (DAT) imaging agents. The corresponding chlorinated analogs were prepared and employed as precursors for radiolabeling leading to the fluorine-18-labeled derivatives via a one-step nucleophilic aliphatic substitution reaction. In vitro binding results showed that the 2 beta-amino compounds 6b, 6d and 7b displayed moderately high affinities to DAT (K-i < 10 nM). Biodistribution studies of [F-18]6b and [F-18]6d showed that the brain uptakes in rats were low. This is likely due to their low lipophilicities. Further structural modifications of these tropane derivatives will be needed to improve their in vivo properties as DAT imaging agents. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.05.030
• 作为产物：
  描述：

  (1R,2S,3S,5S)-8-(2-chloroethyl)-3-(4-chlorophenyl)-N,N-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxamide 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以18%的产率得到1-((1R,2R,3S,5S)-8-(2-chloroethyl)-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]octan-2-yl)-N,N-dimethylmethanamine
  参考文献：
  名称：

  Synthesis and evaluation of novel tropane derivatives as potential PET imaging agents for the dopamine transporter

  摘要：

  A novel series of tropane derivatives containing a fluorinated tertiary amino or amide at the 2 beta position was synthesized, labeled with the positron-emitter fluorine-18 (t(1/2) = 109.8 min), and tested as potential in vivo dopamine transporter (DAT) imaging agents. The corresponding chlorinated analogs were prepared and employed as precursors for radiolabeling leading to the fluorine-18-labeled derivatives via a one-step nucleophilic aliphatic substitution reaction. In vitro binding results showed that the 2 beta-amino compounds 6b, 6d and 7b displayed moderately high affinities to DAT (K-i < 10 nM). Biodistribution studies of [F-18]6b and [F-18]6d showed that the brain uptakes in rats were low. This is likely due to their low lipophilicities. Further structural modifications of these tropane derivatives will be needed to improve their in vivo properties as DAT imaging agents. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.05.030