9-[3-((3R,5S)-3,4,5-Trimethyl-piperazin-1-yl)-propyl]-9H-carbazole | 367275-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 9-[3-((3R,5S)-3,4,5-Trimethyl-piperazin-1-yl)-propyl]-9H-carbazole
• 英文别名: 9-[3-(3,4,5-Trimethyl-piperazin-1-yl)-propyl]-9H-carbazole；9-[3-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]propyl]carbazole
• CAS: 367275-16-9
• 化学式: C₂₂H₂₉N₃
• 分子量: 335.492
• InChiKey: QDBZAAWPKCEIBY-HDICACEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  11.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-[3-((3R,5S)-3,4,5-Trimethyl-piperazin-1-yl)-propyl]-9H-carbazole 在 palladium on activated charcoal 氢气 、 硝酸 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 25.0 ℃ 、206.84 kPa 条件下， 反应 5.5h， 生成 9-[3-((3R,5S)-3,4,5-Trimethyl-piperazin-1-yl)-propyl]-9H-carbazol-3-ylamine
  参考文献：
  名称：

  Isothiocyanate Derivatives of 9-[3-(cis-3,5-Dimethyl-1-piperazinyl)propyl]- carbazole (Rimcazole):  Irreversible Ligands for the Dopamine Transporter

  摘要：

  Cocaine has been reported to bind to the dopamine transporter in a biphasic fashion, and it has been hypothesized that the low-affinity component may play a modulatory role in cocaine's psychomotor stimulant effects. In an effort to gain further insight into the roles of the two sites, we have prepared a series of irreversible ligands based on rimcazole (9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole, 2), a compound that has been postulated to bind only to the low-affinity site. The alkylating moiety (isothiocyanate) is attached to the distal nitrogen of the piperazine ring via alkyl chains of varying lengths or directly attached to one of the aromatic groups. It was found that substitution on the piperazine nitrogen caused an initial decrease in affinity that was recovered as the alkyl chain length increased. Importantly, the analogue 16, with the highest affinity for the dopamine transporter (DAT), binds in a monophasic and irreversible manner, as evidenced by the greatly diminished binding of [H-3]WIN 35,428 in tissue that had been preincubated with the Ligand and then thoroughly washed using centrifugation. The dose-dependent reduction in B-max was accompanied by a concentration-related decrease in K-D values. This shift in K-D to a lower value suggests that the preincubation with 16 produced a preferential irreversible binding to the low-affinity [H-3]WIN 35,428 site on the dopamine transporter. These Ligands may prove to be important tools with which to study the significance of the low-affinity site on the DAT. Since rimcazole does not share the behavioral profile of cocaine, and in fact appears to play a modulatory role, these compounds may provide leads for a novel cocaine-abuse treatment.

  DOI：

  10.1021/jm9705519
• 作为产物：
  描述：

  聚合甲醛 、 rimcazole 在 sodium cyanoborohydride 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 2.0h， 以85%的产率得到9-[3-((3R,5S)-3,4,5-Trimethyl-piperazin-1-yl)-propyl]-9H-carbazole
  参考文献：
  名称：

  Isothiocyanate Derivatives of 9-[3-(cis-3,5-Dimethyl-1-piperazinyl)propyl]- carbazole (Rimcazole):  Irreversible Ligands for the Dopamine Transporter

  摘要：

  Cocaine has been reported to bind to the dopamine transporter in a biphasic fashion, and it has been hypothesized that the low-affinity component may play a modulatory role in cocaine's psychomotor stimulant effects. In an effort to gain further insight into the roles of the two sites, we have prepared a series of irreversible ligands based on rimcazole (9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole, 2), a compound that has been postulated to bind only to the low-affinity site. The alkylating moiety (isothiocyanate) is attached to the distal nitrogen of the piperazine ring via alkyl chains of varying lengths or directly attached to one of the aromatic groups. It was found that substitution on the piperazine nitrogen caused an initial decrease in affinity that was recovered as the alkyl chain length increased. Importantly, the analogue 16, with the highest affinity for the dopamine transporter (DAT), binds in a monophasic and irreversible manner, as evidenced by the greatly diminished binding of [H-3]WIN 35,428 in tissue that had been preincubated with the Ligand and then thoroughly washed using centrifugation. The dose-dependent reduction in B-max was accompanied by a concentration-related decrease in K-D values. This shift in K-D to a lower value suggests that the preincubation with 16 produced a preferential irreversible binding to the low-affinity [H-3]WIN 35,428 site on the dopamine transporter. These Ligands may prove to be important tools with which to study the significance of the low-affinity site on the DAT. Since rimcazole does not share the behavioral profile of cocaine, and in fact appears to play a modulatory role, these compounds may provide leads for a novel cocaine-abuse treatment.

  DOI：

  10.1021/jm9705519

文献信息

• Isothiocyanate Derivatives of 9-[3-(<i>cis-</i>3,5-Dimethyl-1-piperazinyl)propyl]- carbazole (Rimcazole):  Irreversible Ligands for the Dopamine Transporter
  作者：Stephen M. Husbands、Sari Izenwasser、Richard J. Loeloff、Jonathan L. Katz、Wayne D. Bowen、Bertold J. Vilner、Amy Hauck Newman

  DOI：10.1021/jm9705519

  日期：1997.12.1

  Cocaine has been reported to bind to the dopamine transporter in a biphasic fashion, and it has been hypothesized that the low-affinity component may play a modulatory role in cocaine's psychomotor stimulant effects. In an effort to gain further insight into the roles of the two sites, we have prepared a series of irreversible ligands based on rimcazole (9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole, 2), a compound that has been postulated to bind only to the low-affinity site. The alkylating moiety (isothiocyanate) is attached to the distal nitrogen of the piperazine ring via alkyl chains of varying lengths or directly attached to one of the aromatic groups. It was found that substitution on the piperazine nitrogen caused an initial decrease in affinity that was recovered as the alkyl chain length increased. Importantly, the analogue 16, with the highest affinity for the dopamine transporter (DAT), binds in a monophasic and irreversible manner, as evidenced by the greatly diminished binding of [H-3]WIN 35,428 in tissue that had been preincubated with the Ligand and then thoroughly washed using centrifugation. The dose-dependent reduction in B-max was accompanied by a concentration-related decrease in K-D values. This shift in K-D to a lower value suggests that the preincubation with 16 produced a preferential irreversible binding to the low-affinity [H-3]WIN 35,428 site on the dopamine transporter. These Ligands may prove to be important tools with which to study the significance of the low-affinity site on the DAT. Since rimcazole does not share the behavioral profile of cocaine, and in fact appears to play a modulatory role, these compounds may provide leads for a novel cocaine-abuse treatment.