2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane | 281667-94-5

• 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: 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane
• 英文别名: FECNT；Fecnt；methyl (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-(2-fluoroethyl)-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 281667-94-5
• 化学式: C₁₇H₂₁ClFNO₂
• 分子量: 325.811
• InChiKey: YYXOKPOCUHEGJE-JJXSEGSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane 在 盐酸 、 草酰氯 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-(2-fluoroethyl)-8-azabicyclo[3.2.1]octane-2-carbonyl chloride
  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：

  脱水芽子碱甲基酯甲磺酸盐 在 sodium carbonate 、 溶剂黄146 、 锌 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 20.0h， 生成 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane
  参考文献：
  名称：

  合成新型卤素和甲苯磺酰氧基去甲托烷衍生物作为多巴胺转运蛋白 PET 配体 [18F]FECNT 一步合成的有效前体

  摘要：

  氟18 标记的nortropane 衍生物2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) 是一种多巴胺转运蛋白(DAT) 配体。目前，它被认为是正电子发射断层扫描成像的参考。在此，报道了用于 [(18)F]FECNT 一步放射合成的新型前体（N-甲苯磺酰氧基-、氯-和溴-类似物）的合成。在一步放射合成中使用 N-甲磺酰氧基前体，获得了粗 [(18)F]FECNT，放射性标记率为 45±10%，证实了这种方法在设计新型标记前体方面的实际效率.

  DOI：

  10.1002/jlcr.3181

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.
• Synthesis of novel halo and tosyloxy nortropane derivatives as efficient precursors for the one-step synthesis of the dopamine transporter PET ligand [¹⁸F]FECNT
  作者：J. Pijarowska-Kruszyna、A. W. Jaron、A. Kachniarz、K. Kasprzak、A. Kowalska、B. Malkowski、S. Demphel、F. Dollé、R. Mikolajczak

  DOI：10.1002/jlcr.3181

  日期：2014.3

  nortropane derivative 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) is a dopamine transporter (DAT) ligand. Currently, it is considered as reference for positron emission tomography imaging. Herein, the synthesis of novel precursors (N-tosyloxy-, chloro-, and bromo- analogues) for one-step radiosynthesis of [(18)F]FECNT is reported. Using the N-mesyloxy- precursor in a one-step

  氟18 标记的nortropane 衍生物2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) 是一种多巴胺转运蛋白(DAT) 配体。目前，它被认为是正电子发射断层扫描成像的参考。在此，报道了用于 [(18)F]FECNT 一步放射合成的新型前体（N-甲苯磺酰氧基-、氯-和溴-类似物）的合成。在一步放射合成中使用 N-甲磺酰氧基前体，获得了粗 [(18)F]FECNT，放射性标记率为 45±10%，证实了这种方法在设计新型标记前体方面的实际效率.