(R)-N,N-di-n-propyl-6,7,8,9-tetrahydro-3H-benzindol-8-ylamine | 149884-86-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (R)-N,N-di-n-propyl-6,7,8,9-tetrahydro-3H-benzindol-8-ylamine
• 英文别名: (R)-6,7,8,9-tetrahydro-N,N-dipropyl-3H-benzindol-8-amine；Dipropyl-(R)-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-yl-amine；(8R)-N,N-dipropyl-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-amine
• CAS: 149884-86-6
• 化学式: C₁₈H₂₆N₂
• 分子量: 270.418
• InChiKey: GKDJCOLVXBCNNK-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-N,N-di-n-propyl-6,7,8,9-tetrahydro-3H-benzindol-8-ylamine 在 氨 作用下， 以 乙醚 为溶剂， 反应 20.67h， 生成 2-((R)-8-Dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indol-1-yl)-2-oxo-acetamide
  参考文献：
  名称：

  8-氨基-6,7,8,9-四氢-3H-苯并[e]吲哚环系统中的结构活性关系。1.芳香族系统中取代基对5-羟色胺和多巴胺受体亚型的影响。

  摘要：

  一系列针对5-（1-丙基氨基）-6,7,8,9-四氢-3H-苯并[e]吲哚-1-甲醛的有效5-HT1A的1-，3-和4-取代基（5 ）制备并在5-HT1A，5-HT1Dα，5-HT1Dβ，D2和D3受体上进行体外测试，并在利血平预处理的大鼠中进行5-HTP和DOPA积累测定中的激动剂活性体内测试。一些化合物已解决。从主成分分析（PCA）图中选择在1位使用的取代基，该图由列表变量和通过半经验方法（PM3）和分子力学软件（MMX）计算的变量构成。在制备的类似物中，一些例如化合物21就5-HT1A作用而言与化合物5等价。所有化合物都对5-HT1A受体具有选择性，

  DOI：

  10.1021/jm00012a021
• 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 作用下， 以 甲醇 、 乙醚 、 硝基甲烷 、 水 为溶剂， 反应 19.0h， 生成 (R)-N,N-di-n-propyl-6,7,8,9-tetrahydro-3H-benzindol-8-ylamine
  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。
• 6,7,8,9-Tetrahydro-N,N-di-n-propyl-3H-benzindol-8-amines. Derivatives as Potent and Orally Active Serotonin 5-HT1A Receptor Agonists
  作者：Peter Stjernloef、Thomas Elebring、Jonas Nilsson、Bengt Andersson、Soeren Lagerkvist、Kjell Svensson、Agneta Ekman、Arvid Carlsson、Haakan Wikstroem

  DOI：10.1021/jm00046a010

  日期：1994.9

  Derivatives and isosteric derivatives of the potent 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole- 1-carbaldehyde (5) were prepared and evaluated in vivo and in vitro for serotonergic and dopaminergic activity. The 1-cyano analog 8 was found to be almost equipotent to 5 and the previously described 2-cyano derivative 6, while a I-chloro and 1-(1,1,1-trifluoroethyl) substituent (9 and 10, respectively) formed less potent derivatives. The isosteric 6,7,8,9-tetrahydro-1H-benz[g]indoles 4 and 12-15 showed surprisingly low affinity or activity at both serotonergic and dopaminergic systems. The interpretations of these results by means of drug-receptor interactions at the 5-HT1A subtype are discussed. Compounds 6 and 8 were found to have high oral bioavailability in the rat (63% and 54%, respectively).
• Stjernloef Peter, Elebring Thomas, Nilsson Jonas, Andersson Bengt, Lagerk+, J. Med. Chem, 37 (1994) N 20, S 3263-3273
  作者：Stjernloef Peter, Elebring Thomas, Nilsson Jonas, Andersson Bengt, Lagerk+

  DOI：——

  日期：——
• (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.
• Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes
  作者：Peter Stjernloef、Michael D. Ennis、Lars O. Hansson、Robert L. Hoffman、Nabil B. Ghazal、Staffan Sundell、Martin W. Smith、Kjell Svensson、Arvid Carlsson、Hkan Wikstroem

  DOI：10.1021/jm00012a021

  日期：1995.6

  compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or

  一系列针对5-（1-丙基氨基）-6,7,8,9-四氢-3H-苯并[e]吲哚-1-甲醛的有效5-HT1A的1-，3-和4-取代基（5 ）制备并在5-HT1A，5-HT1Dα，5-HT1Dβ，D2和D3受体上进行体外测试，并在利血平预处理的大鼠中进行5-HTP和DOPA积累测定中的激动剂活性体内测试。一些化合物已解决。从主成分分析（PCA）图中选择在1位使用的取代基，该图由列表变量和通过半经验方法（PM3）和分子力学软件（MMX）计算的变量构成。在制备的类似物中，一些例如化合物21就5-HT1A作用而言与化合物5等价。所有化合物都对5-HT1A受体具有选择性，