(1R,2S,3S,5S)-3-(4-chlorophenyl)-8-(2-fluoroethyl)-N,N-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxamide | 1384179-43-4

• 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: (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-(2-fluoroethyl)-N,N-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxamide
• CAS: 1384179-43-4
• 化学式: C₁₈H₂₄ClFN₂O
• 分子量: 338.853
• InChiKey: AMQSLZSYEJWDRW-HZMVEIRTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-(2-fluoroethyl)-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71%的产率得到1-[(1R,2R,3S,5S)-3-(4-chlorophenyl)-8-(2-fluoroethyl)-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：

  甲基(1R)-3-(4-氯苯基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-羧酸酯 在 盐酸 、 草酰氯 、 1-氯乙基氯甲酸酯 、 水 、 三乙胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 46.0h， 生成 (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-(2-fluoroethyl)-N,N-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxamide
  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

文献信息

• Synthesis and evaluation of novel tropane derivatives as potential PET imaging agents for the dopamine transporter
  作者：Hongwen Qiao、Lin Zhu、Brian P. Lieberman、Zhihao Zha、Karl Plössl、Hank F. Kung

  DOI：10.1016/j.bmcl.2012.05.030

  日期：2012.7

  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.