(+)-9-O-desmethyl-α-dihydrotetrabenzine | 1214267-79-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (+)-9-O-desmethyl-α-dihydrotetrabenzine
• 英文别名: (2R, 3R, 11bR)-9-O-desmethyldihydrotetrabenazine；DK3H75E8YD；(2R,3R,11bR)-9-methoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizine-2,10-diol
• CAS: 1214267-79-4；1214267-56-7
• 化学式: C₁₈H₂₇NO₃
• 分子量: 305.417
• InChiKey: QPCCFQGYORNUSE-FVQBIDKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  52.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 (+)-9-O-desmethyl-α-dihydrotetrabenzine 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (+)-α-[11C]dihydrotetrabenazine
  参考文献：
  名称：

  一种新型的用于2型囊泡单胺转运蛋白的潜在正电子发射断层显像剂。

  摘要：

  在1990年代初期，显示9-（+）-11C-二氢丁苯那嗪（9-（+）-11C-DTBZ）是用于各种神经退行性疾病的有用的正电子发射断层扫描（PET）成像剂。在这里，我们描述了作为囊泡单胺转运蛋白2（VMAT2）成像剂的9-（+）-11C-DTBZ类似物10-（+）-11C-DTBZ的放射合成和评估，并将其与9-（+ ）-11C-DTBZ。在5M NaOH的存在下，通过其10羟基前体的11C-MeI甲基化获得10-（+）-11C-DTBZ。与9-（+）-11C-DTBZ（30.5±2.3％）相比，它的平均放射化学产率为35.3±3.6％（经衰变校正至合成结束（EOS））略好。MicroPET研究表明，注射后40分钟，10-（+）-11C-DTBZ的纹状体与小脑的比率为3.74±0.21，而9-（+）-11C-DTBZ的比率为2.50±0.33。这表明10-（+）-11C-DTBZ在富含VMA

  DOI：

  10.1371/journal.pone.0161295
• 作为产物：
  描述：

  3-异丁基-9,10-二甲氧基-1,3,4,6,7,11b-六氢-2H-吡啶并[2,1-a]异喹啉-2-酮 生成 (+)-9-O-desmethyl-α-dihydrotetrabenzine
  参考文献：
  名称：

  Binding of α-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific

  摘要：

  The two enantiomers of alpha-dihydrotetrabenazine were separated using chiral high performance liquid chromatography. The (+)-isomer showed high affinity in vitro (K-i=0.97+/-0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (K-i=2.2+/-0.3 mu M). Each isomer was then synthesized in carbon-ii labeled form, and regional brain biodistributions in mice determined after intravenous injection. Only (+)-alpha-dihydrotetrabenazine showed selective and specific accumulations in regions of dense monoaminergic innervation (e.g., striatum, hypothalamus), which could be blocked by coinjection of unlabeled tetrabenazine. Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is thus stereospecific.

  DOI：

  10.1016/0014-2999(95)00162-e

文献信息

• PHARMACEUTICAL COMPOUNDS
  申请人：Duffield Andrew John

  公开号：US20100087475A1

  公开（公告）日：2010-04-08

  This application describes substituted 1,3,4,6,7,11b-hexahydro-benzo(a)quinolizine compounds, pharmaceutical compositions containing them, processes for making them and their therapeutic methods.

  该应用程序描述了取代的1,3,4,6,7,11b-六氢苯并(a)喹啉化合物，含有它们的药物组合物，制备它们的方法以及它们的治疗方法。
• A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2
  作者：Zih-Rou Huang、Chia-Ling Tsai、Ya-Yao Huang、Chyng-Yann Shiue、Kai-Yuan Tzen、Ruoh-Fang Yen、Ling-Wei Hsin

  DOI：10.1371/journal.pone.0161295

  日期：——

  radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did

  在1990年代初期，显示9-（+）-11C-二氢丁苯那嗪（9-（+）-11C-DTBZ）是用于各种神经退行性疾病的有用的正电子发射断层扫描（PET）成像剂。在这里，我们描述了作为囊泡单胺转运蛋白2（VMAT2）成像剂的9-（+）-11C-DTBZ类似物10-（+）-11C-DTBZ的放射合成和评估，并将其与9-（+ ）-11C-DTBZ。在5M NaOH的存在下，通过其10羟基前体的11C-MeI甲基化获得10-（+）-11C-DTBZ。与9-（+）-11C-DTBZ（30.5±2.3％）相比，它的平均放射化学产率为35.3±3.6％（经衰变校正至合成结束（EOS））略好。MicroPET研究表明，注射后40分钟，10-（+）-11C-DTBZ的纹状体与小脑的比率为3.74±0.21，而9-（+）-11C-DTBZ的比率为2.50±0.33。这表明10-（+）-11C-DTBZ在富含VMA
• Binding of α-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific
  作者：Michael Kilbourn、Lihsueh Lee、Thierry Vander Borght、Douglas Jewett、Kirk Frey

  DOI：10.1016/0014-2999(95)00162-e

  日期：1995.5

  The two enantiomers of alpha-dihydrotetrabenazine were separated using chiral high performance liquid chromatography. The (+)-isomer showed high affinity in vitro (K-i=0.97+/-0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (K-i=2.2+/-0.3 mu M). Each isomer was then synthesized in carbon-ii labeled form, and regional brain biodistributions in mice determined after intravenous injection. Only (+)-alpha-dihydrotetrabenazine showed selective and specific accumulations in regions of dense monoaminergic innervation (e.g., striatum, hypothalamus), which could be blocked by coinjection of unlabeled tetrabenazine. Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is thus stereospecific.