(S)-(-)-1-formyl-6,7,8,9-tetrahydro-N,N-dipropyl-3H-benzindol-8-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (S)-(-)-1-formyl-6,7,8,9-tetrahydro-N,N-dipropyl-3H-benzindol-8-amine
• 英文别名: (-)-U 89968E；(S)-8-Dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indole-1-carbaldehyde；(8S)-8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benzo[e]indole-1-carbaldehyde
• 化学式: C₁₉H₂₆N₂O
• 分子量: 298.428
• InChiKey: DSEPKSLFXGYPIU-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  8-chloro-2-(N-n-propyl-N-propionyl-amino)-1,2,3,4-tetrahydronaphthalene 在 palladium on activated charcoal lithium aluminium tetrahydride 、 硫酸 、 盐酸羟胺 、 硝酸 、 甲酸铵 、 sodium sulfate 、 三氯氧磷 作用下， 以 甲醇 、 乙醚 、 硝基甲烷 、 水 为溶剂， 反应 20.17h， 生成 (S)-(-)-1-formyl-6,7,8,9-tetrahydro-N,N-dipropyl-3H-benzindol-8-amine
  参考文献：
  名称：

  (S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde: a new class of orally active 5-HT1A-receptor agonists

  摘要：

  The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8-amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n-propylamino)tetrahydronaphthalene (8-OH-DPAT). In contrast to 8-OH-DPAT, the enantiomers of compound 6 were found to have good oral availability.

  DOI：

  10.1021/jm00067a002

文献信息

• Synthesis of (<i>r</i>)- and (<i>s</i>)-1-formyl-6,7,8,9-tetrahydro-<i>N,N</i>-(dipropyl)-3<i>H</i>-benz[<i>e</i>]indol-8-amines: Potent and orally active 5-ht_1areceptor agonists
  作者：Chiu-Hong Lin、Michael D. Ennis、Robert L. Hoffman、Gillian Phillips、Susanne R. Haadsma-Svensson、Nabil B. Ghazal、Connie G. Chidester

  DOI：10.1002/jhet.5570310123

  日期：1994.1

  An efficient synthesis of the potent and orally active 5-HT1A agonists, (R)-(+)- and (S)-(-)-1-formyl-6,7,8,9-tetrahydro-N,N-dipropyl-3H-benz[e]indol-8-amines 1a and 1b, is described. This synthesis was accomplished in twelve steps from commercially available 1,5,6,7-tetrahydro-4H-indol-4-one (5). The key step involved a regio-controlled Friedel-Crafts acylation of 1-(p-toluenesulfonyl)indol-4-acetyl

  的强有力的和口服活性的5-HT的高效合成1A激动剂，（- [R ）- （+） -和（小号） - （ - ） - 1-甲酰基-6,7,8,9-四氢- N，N- -描述了二丙基-3 H-苯并[ e ]吲哚-8-胺1a和1b。从市售的1,5,6,7-四氢-4 H-吲哚-4-酮（5）以十二个步骤完成该合成。关键步骤包括将区域控制的1-（对甲苯磺酰基）吲哚-4-乙酰氯与乙烯的弗里德-克来夫斯酰化反应，以制得通用的合成子3-（对甲苯磺酰基）-6,7,8,9- tetrahydro-3 H -benz [e ]吲哚-8-一（10）。随后将该酮与手性α-甲基苄基胺在还原性胺化条件下偶联，得到非对映异构体的混合物。这些非对映异构体通过色谱法或衍生的盐酸盐的分步重结晶有效分离。纯非对映异构体的脱苄基作用后，进行烷基化和甲酰化反应，制得纯度> 99％的（R）-（+）-和（S）-（-）-对映体1a和1b。
• (S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde: a new class of orally active 5-HT1A-receptor agonists
  作者：Peter Stjernloef、Maria Gullme、Thomas Elebring、Bengt Andersson、Haakan Wikstroem、Soeren Lagerquist、Kjell Svensson、Agneta Ekman、Arvid Carlsson、Staffan Sundell

  DOI：10.1021/jm00067a002

  日期：1993.7

  The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8-amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n-propylamino)tetrahydronaphthalene (8-OH-DPAT). In contrast to 8-OH-DPAT, the enantiomers of compound 6 were found to have good oral availability.