2α-isopropyl-2β-hydroxy-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH-benzoquinolizine

• 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: 2α-isopropyl-2β-hydroxy-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH-benzoquinolizine
• 英文别名: (2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-2-propan-2-yl-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-ol
• 化学式: C₂₂H₃₅NO₃
• 分子量: 361.525
• InChiKey: RSWJAUTXEACVDJ-SFGWALBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

上下游信息

反应信息

• 作为产物：
  描述：

  异丙基锂 、 丁苯那嗪 在 水 作用下， 生成 2α-isopropyl-2β-hydroxy-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH-benzoquinolizine
  参考文献：
  名称：

  In Vitro and in Vivo Studies of Benzisoquinoline Ligands for the Brain Synaptic Vesicle Monoamine Transporter

  摘要：

  Tetrabenazine is a high-affinity inhibitor of the vesicular monoamine transporter in mammalian brain. As part of a program to develop in vivo imaging agents for these transporters in human brain, a series of 2-alkylated dihydrotetrabenazine ligands was synthesized and evaluated in vitro and in. vivo for binding to the brain vesicular monoamine transporter. Additions of organometallic reagents to tetrabenazine produced 2-methyl, 2-ethyl, 2-n-propyl, 2-isopropyl, and 2-isobutyl derivatives of dihydrotetrabenazine. The stereochemistry and conformation of the addition products were thoroughly verified by two-dimensional NMR techniques. All of these alkyl derivatives displayed in vitro affinity. for the vesicular monoamine transporter binding site in rat brain using competitive assays with the radioligand [H-3]methoxytetrabenazine. Except for the isopropyl derivative, all compounds when tested at 10 mg/kg iv showed an ability to inhibit in vivo accumulation of the radioligand [C-11]methoxytetrabenazine in the mouse brain striatum. Derivatives with small alkyl groups (methyl, ethyl) were more effective than those with large groups (propyl, isobutyl). These studies suggest that large groups in the 2-position of the benzisoquinoline structure will significantly diminish both in vitro and in vivo binding of these compounds to the vesicular monoamine transporter.

  DOI：

  10.1021/jm950117b

文献信息

• <i>In Vitro</i> and <i>in Vivo</i> Studies of Benzisoquinoline Ligands for the Brain Synaptic Vesicle Monoamine Transporter
  作者：Lihsueh C. Lee、Thierry Vander Borght、Phillip S. Sherman、Kirk A. Frey、Michael R. Kilbourn

  DOI：10.1021/jm950117b

  日期：1996.1.1

  Tetrabenazine is a high-affinity inhibitor of the vesicular monoamine transporter in mammalian brain. As part of a program to develop in vivo imaging agents for these transporters in human brain, a series of 2-alkylated dihydrotetrabenazine ligands was synthesized and evaluated in vitro and in. vivo for binding to the brain vesicular monoamine transporter. Additions of organometallic reagents to tetrabenazine produced 2-methyl, 2-ethyl, 2-n-propyl, 2-isopropyl, and 2-isobutyl derivatives of dihydrotetrabenazine. The stereochemistry and conformation of the addition products were thoroughly verified by two-dimensional NMR techniques. All of these alkyl derivatives displayed in vitro affinity. for the vesicular monoamine transporter binding site in rat brain using competitive assays with the radioligand [H-3]methoxytetrabenazine. Except for the isopropyl derivative, all compounds when tested at 10 mg/kg iv showed an ability to inhibit in vivo accumulation of the radioligand [C-11]methoxytetrabenazine in the mouse brain striatum. Derivatives with small alkyl groups (methyl, ethyl) were more effective than those with large groups (propyl, isobutyl). These studies suggest that large groups in the 2-position of the benzisoquinoline structure will significantly diminish both in vitro and in vivo binding of these compounds to the vesicular monoamine transporter.