4,4-Dimethyl-1-(4-{propyl-[3-(toluene-4-sulfonyl)-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-yl]-amino}-butyl)-piperidine-2,6-dione | 163561-73-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 4,4-Dimethyl-1-(4-{propyl-[3-(toluene-4-sulfonyl)-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-yl]-amino}-butyl)-piperidine-2,6-dione
• 英文别名: 4,4-Dimethyl-1-[4-[[3-(4-methylphenyl)sulfonyl-6,7,8,9-tetrahydrobenzo[e]indol-8-yl]-propylamino]butyl]piperidine-2,6-dione
• CAS: 163561-73-7
• 化学式: C₃₃H₄₃N₃O₄S
• 分子量: 577.788
• InChiKey: PLJCOWQKQDFQFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,4-Dimethyl-1-(4-{propyl-[3-(toluene-4-sulfonyl)-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-yl]-amino}-butyl)-piperidine-2,6-dione 在 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以54%的产率得到4,4-Dimethyl-1-{4-[propyl-(6,7,8,9-tetrahydro-3H-benzo[e]indol-8-yl)-amino]-butyl}-piperidine-2,6-dione
  参考文献：
  名称：

  Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 2: Effect of 8-Amino Nitrogen Substitution on Serotonin Receptor Binding and Pharmacology

  摘要：

  A series of analogs of the potent and selective 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (2b) (OSU191) was prepared in which the dipropylamino group was modified to bear a variety of substituents. These compounds were evaluated for both in vitro and in vivo effects, including the establishment of a receptor binding profile for these analogs at the 5-HT1A, dopamine D-2, dopamine D-3, 5-HT1D alpha, and 5-HT1D beta sites. Several of the analogs were evaluated for their biochemical effects in reserpinized rats, specifically with regard to in vivo changes in brain levels of 5-HTP and DOPA. Nearly all of the compounds prepared for this study were exceedingly potent at the 5-HT1A receptor, although most also displayed significant affinity for the dopamine D-2 receptor. A strong preference for the 5-HT1D alpha, over the 5-HT1D beta receptor was also apparent. An analog bearing a butylglutarimide side chain, S-7k, was extremely selective for the 5-HT1A receptor. Although this compound possessed a K-i of 0.6 nM, it elicited only modest changes in 5-HTP brain levels. However, this compound did not appear as an antagonist when tested in a cyclic-AMP-based intrinsic activity assay.

  DOI：

  10.1021/jm00012a022
• 作为产物：
  描述：

  3-(p-toluenesulfonyl)-6,7,8,9-tetrahydro-3H-benzindol-8-one 在 sodium cyanoborohydride 、 sodium carbonate 、 对甲苯磺酸 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 4,4-Dimethyl-1-(4-{propyl-[3-(toluene-4-sulfonyl)-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-yl]-amino}-butyl)-piperidine-2,6-dione
  参考文献：
  名称：

  Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 2: Effect of 8-Amino Nitrogen Substitution on Serotonin Receptor Binding and Pharmacology

  摘要：

  A series of analogs of the potent and selective 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (2b) (OSU191) was prepared in which the dipropylamino group was modified to bear a variety of substituents. These compounds were evaluated for both in vitro and in vivo effects, including the establishment of a receptor binding profile for these analogs at the 5-HT1A, dopamine D-2, dopamine D-3, 5-HT1D alpha, and 5-HT1D beta sites. Several of the analogs were evaluated for their biochemical effects in reserpinized rats, specifically with regard to in vivo changes in brain levels of 5-HTP and DOPA. Nearly all of the compounds prepared for this study were exceedingly potent at the 5-HT1A receptor, although most also displayed significant affinity for the dopamine D-2 receptor. A strong preference for the 5-HT1D alpha, over the 5-HT1D beta receptor was also apparent. An analog bearing a butylglutarimide side chain, S-7k, was extremely selective for the 5-HT1A receptor. Although this compound possessed a K-i of 0.6 nM, it elicited only modest changes in 5-HTP brain levels. However, this compound did not appear as an antagonist when tested in a cyclic-AMP-based intrinsic activity assay.

  DOI：

  10.1021/jm00012a022