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

文献信息

• 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
  作者：Dongxia Xing、Ping Chen、Robert Keil、Clinton D. Kilts、Bing Shi、Vernon M. Camp、Gene Malveaux、Timothy Ely、Michael J. Owens、John Votaw、Margaret Davis、John M. Hoffman、Roy A. E. BaKay、Thygarajan Subramanian、Ray L. Watts、Mark M. Goodman

  DOI：10.1021/jm9902234

  日期：2000.2.1

  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.