cis-10-bromo-1,2,3,5,6,10b-hexahydro-6-<4-(methylthio)phenyl>pyrrolo<2,1-a>isoquinoline | 129540-07-4

• 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: cis-10-bromo-1,2,3,5,6,10b-hexahydro-6-<4-(methylthio)phenyl>pyrrolo<2,1-a>isoquinoline
• 英文别名: trans-10-bromo-1,2,3,5,6,10b-hexahydro-6-<4-(methylthio)phenyl>pyrrolo<2,1-a>isoquinoline；trans-10-bromo-1,2,3,5,6,10b-hexahydro-6-[4-(methylthio)phenyl]pyrrolo[2,1-a]isoquinoline
• CAS: 129540-07-4
• 化学式: C₁₉H₂₀BrNS
• 分子量: 374.345
• InChiKey: MPPAAPYUXHGYGD-AEFFLSMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.45
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  3.24
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  氰化亚铜 、 cis-10-bromo-1,2,3,5,6,10b-hexahydro-6-<4-(methylthio)phenyl>pyrrolo<2,1-a>isoquinoline 在 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66%的产率得到trans-1,2,3,5,6,10b-hexahydro-6-<4-(methylthio)phenyl>pyrrolo<2,1-a>isoquinoline-10-carbonitrile
  参考文献：
  名称：

  Pyrroloisoquinoline antidepressants. 3. A focus on serotonin

  摘要：

  A collection of hexahydropyrroloisoquinoline derivatives (1-22), which represent a class of compounds that inhibit the neuronal uptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT), was investigated in vivo for serotonin-potentiating properties in the mouse head-twitch and rat serotonin syndrome assays. The p-methylthio compound 3b (McN-5652-Z) was found to possess exceptional activity in these assays, and the activity was attributable almost exclusively to the (+)-6S,10bR enantiomer. Ten closely related analogues were synthesized, tested, and compared among themselves and with some previously prepared compounds, both in vivo and in vitro. Several trans diastereomers exhibited strong inhibition of 5-HT uptake and substantial potentiation of 5-HT, while the cis diastereomers (3a, 4a, and 10a) tested were virtually devoid of such activity. Although 3b was only moderately selective in inhibiting the uptake of 5-HT vs NE, its 10-substituted analogues 4b, 7b-9b had improved 5-HT selectivity relative to NE, to the extent of 20-25 times (150-200 times relative to DA). Of these more selective compounds (in vitro), only 4b and 7b had substantial activity in vivo. Sulfoxide 11b appeared to function as a prodrug of 3b in vivo.

  DOI：

  10.1021/jm00172a018
• 作为产物：
  描述：

  2-(2-bromophenyl)-1-pyrroline 在 sodium hydroxide 、 sodium tetrahydroborate 、 PPA 、 硼烷四氢呋喃络合物 作用下， 反应 0.5h， 生成 cis-10-bromo-1,2,3,5,6,10b-hexahydro-6-<4-(methylthio)phenyl>pyrrolo<2,1-a>isoquinoline
  参考文献：
  名称：

  Pyrroloisoquinoline antidepressants. 3. A focus on serotonin

  摘要：

  A collection of hexahydropyrroloisoquinoline derivatives (1-22), which represent a class of compounds that inhibit the neuronal uptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT), was investigated in vivo for serotonin-potentiating properties in the mouse head-twitch and rat serotonin syndrome assays. The p-methylthio compound 3b (McN-5652-Z) was found to possess exceptional activity in these assays, and the activity was attributable almost exclusively to the (+)-6S,10bR enantiomer. Ten closely related analogues were synthesized, tested, and compared among themselves and with some previously prepared compounds, both in vivo and in vitro. Several trans diastereomers exhibited strong inhibition of 5-HT uptake and substantial potentiation of 5-HT, while the cis diastereomers (3a, 4a, and 10a) tested were virtually devoid of such activity. Although 3b was only moderately selective in inhibiting the uptake of 5-HT vs NE, its 10-substituted analogues 4b, 7b-9b had improved 5-HT selectivity relative to NE, to the extent of 20-25 times (150-200 times relative to DA). Of these more selective compounds (in vitro), only 4b and 7b had substantial activity in vivo. Sulfoxide 11b appeared to function as a prodrug of 3b in vivo.

  DOI：

  10.1021/jm00172a018