2β-carbo-(R)-1'-mesyl-2-propoxy-3β-(4-chlorophenyl)tropane | 262423-82-5

• 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-carbo-(R)-1'-mesyl-2-propoxy-3β-(4-chlorophenyl)tropane
• 英文别名: [(2R)-1-methylsulfonyloxypropan-2-yl] (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 262423-82-5
• 化学式: C₁₉H₂₆ClNO₅S
• 分子量: 415.938
• InChiKey: DOPCVYWEJLUFRI-WRJYRGCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2β-carbo-(R)-1'-mesyl-2-propoxy-3β-(4-chlorophenyl)tropane 在 potassium [¹⁸F]fluoride 、 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 乙腈 为溶剂， 反应 0.17h， 生成 2β-carbo-(R-1'-[18F]fluoro-2-propoxy)-3β-(4-chlorophenyl)tropane
  参考文献：
  名称：

  Synthesis, Biodistribution, and Primate Imaging of Fluorine-18 Labeled 2β-Carbo-1‘-fluoro-2-propoxy-3β-(4-chlorophenyl)tropanes. Ligands for the Imaging of Dopamine Transporters by Positron Emission Tomography

  摘要：

  2 beta-(R)-Carbo-1-fluoro-2-propoxy-3 beta-(4-chlorophenyl)tropane ((R)-FIPCT, R-6) and 2 beta-(S)-carbo-1-fluoro-2-propoxy-3 beta-(4-chlorophenyl)tropane ((S)-FIPCT, S-6) were prepared and evaluated in vitro and in vivo for dopamine transporter (DAT) selectivity and specificity. High specific activity [F-18](R)-FIPCT and [F-18](S)-FIPCT were synthesized in 5% radiochemical yield (decay-corrected to end of bombardment (EOB)) by preparation of the precursors 2 beta-carbo-R-1-mesyloxy-2-propoxy-3 beta-(4-chlorophenyl)tr (R-12) and 2 beta-carbo-S-1-mesyloxy-2-propoxy-3 beta-(4-chlorophenyl)tropane (S-12) followed by treatment with no carrier-added potassium[F-18]-fluoride and kyrptofix K222 in acetonitrile. Competition binding in cells stably expressing the transfected human DAT and serotonin transporter (SERT) labeled by [H-3]WIN 35428 and [H-3]-citalopram, respectively, demonstrated the following order of DAT affinity (K-i in nM): GBR 12909 (0.36) > CIT(0.48) > (S)-FIPCT(0.67) much greater than (R)-FIPCT (3.2). The affinity of(S)-FIPCT and (R)-FIPCT for SERT was 127- and 20-fold lower, respectively, than for DAT. In vivo biodistribution studies were performed in male rats and demonstrated that the brain uptake of [F-18](R)-FIPCT and [F-18](S)-FIPCT were selective and specific for DAT rich regions (caudate and putamen). PET brain imaging studies in monkeys demonstrated high [F-18](R)-FIPCT and [F-18](S)-FIPCT uptake in the caudate and putamen which resulted in caudate-to-cerebellum and putamen-to-cerebellum ratios of 2.5-3.5 at 115 min. [F-18](R)-FIPCT uptake in the caudate/putamen achieved transient equilibrium at 75 min. In an imaging experiment with [F-18](S)-FIPCT in a rhesus monkey with its left hemisphere lesioned with MPTP, radioactivity was reduced to background in the caudate and putamen of the lesioned hemisphere. The high specific activity one-step radiolabeling preparation and high specificity and selectivity of [F-18](R)-FIPCT and [F-18](S)-FIPCT for DAT indicate [F-18](R)-FIPCT and [F-18](S)-FIPCT are potential radioligands for mapping brain DAT in humans using PET.

  DOI：

  10.1021/jm9902234
• 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 水 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 76.0h， 生成 2β-carbo-(R)-1'-mesyl-2-propoxy-3β-(4-chlorophenyl)tropane
  参考文献：
  名称：

  Synthesis, Biodistribution, and Primate Imaging of Fluorine-18 Labeled 2β-Carbo-1‘-fluoro-2-propoxy-3β-(4-chlorophenyl)tropanes. Ligands for the Imaging of Dopamine Transporters by Positron Emission Tomography

  摘要：

  2 beta-(R)-Carbo-1-fluoro-2-propoxy-3 beta-(4-chlorophenyl)tropane ((R)-FIPCT, R-6) and 2 beta-(S)-carbo-1-fluoro-2-propoxy-3 beta-(4-chlorophenyl)tropane ((S)-FIPCT, S-6) were prepared and evaluated in vitro and in vivo for dopamine transporter (DAT) selectivity and specificity. High specific activity [F-18](R)-FIPCT and [F-18](S)-FIPCT were synthesized in 5% radiochemical yield (decay-corrected to end of bombardment (EOB)) by preparation of the precursors 2 beta-carbo-R-1-mesyloxy-2-propoxy-3 beta-(4-chlorophenyl)tr (R-12) and 2 beta-carbo-S-1-mesyloxy-2-propoxy-3 beta-(4-chlorophenyl)tropane (S-12) followed by treatment with no carrier-added potassium[F-18]-fluoride and kyrptofix K222 in acetonitrile. Competition binding in cells stably expressing the transfected human DAT and serotonin transporter (SERT) labeled by [H-3]WIN 35428 and [H-3]-citalopram, respectively, demonstrated the following order of DAT affinity (K-i in nM): GBR 12909 (0.36) > CIT(0.48) > (S)-FIPCT(0.67) much greater than (R)-FIPCT (3.2). The affinity of(S)-FIPCT and (R)-FIPCT for SERT was 127- and 20-fold lower, respectively, than for DAT. In vivo biodistribution studies were performed in male rats and demonstrated that the brain uptake of [F-18](R)-FIPCT and [F-18](S)-FIPCT were selective and specific for DAT rich regions (caudate and putamen). PET brain imaging studies in monkeys demonstrated high [F-18](R)-FIPCT and [F-18](S)-FIPCT uptake in the caudate and putamen which resulted in caudate-to-cerebellum and putamen-to-cerebellum ratios of 2.5-3.5 at 115 min. [F-18](R)-FIPCT uptake in the caudate/putamen achieved transient equilibrium at 75 min. In an imaging experiment with [F-18](S)-FIPCT in a rhesus monkey with its left hemisphere lesioned with MPTP, radioactivity was reduced to background in the caudate and putamen of the lesioned hemisphere. The high specific activity one-step radiolabeling preparation and high specificity and selectivity of [F-18](R)-FIPCT and [F-18](S)-FIPCT for DAT indicate [F-18](R)-FIPCT and [F-18](S)-FIPCT are potential radioligands for mapping brain DAT in humans using PET.

  DOI：

  10.1021/jm9902234