N,N-di-n-propyl-5,6,7,8-tetrahydrobenzindol-7-amine | 149835-32-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: N,N-di-n-propyl-5,6,7,8-tetrahydrobenzindol-7-amine
• 英文别名: N,N-di-n-propyl-5,6,7,8-tetrahydro-1H-benzindol-7-ylamine；1H-Benz(f)indol-7-amine, 5,6,7,8-tetrahydro-N,N-dipropyl-；N,N-dipropyl-5,6,7,8-tetrahydro-1H-benzo[f]indol-7-amine
• CAS: 149835-32-5
• 化学式: C₁₈H₂₆N₂
• 分子量: 270.418
• InChiKey: PJRCRPZYNQZZBV-UHFFFAOYSA-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：

  N,N-二甲基甲酰胺 、 N,N-di-n-propyl-5,6,7,8-tetrahydrobenzindol-7-amine 在 三氯氧磷 作用下， 以21%的产率得到7-(di-n-propylamino)-5,6,7,8-tetrahydro-1H-benzindole-3-carbaldehyde
  参考文献：
  名称：

  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

  摘要：

  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).

  DOI：

  10.1021/jm00046a010
• 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 N,N-di-n-propyl-5,6,7,8-tetrahydrobenzindol-7-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 and evaluation of N,N-di-n-propyltetrahydrobenz[f]indol-7-amine and related congeners as dopaminergic agonists
  作者：David E. Nichols、John M. Cassady、Paul E. Persons、Ming C. Yeung、James A. Clemens、E. Barry Smalstig

  DOI：10.1021/jm00129a017

  日期：1989.9

  chain, compounds with the indole N-H located in the other "meta" position (i.e. 4-[2-(di-n-propylamino)ethyl]indole (2) or its rigid benz[e]indole analogue 3) were much more potent dopamine agonists. The results argue for a particular orientation of the indole N-H vector. In addition, relatively potent dopamine agonists also resulted when the pyrrole portion of the indole ring was replaced by a methanesulfonamido

  对6- [2-（二-正丙基氨基）乙基]吲哚（4），其刚性类似物N，N-二正丙基-5,6,7,8-四氢苯并[f]吲哚-7的评估在抑制多巴胺能活性的体内模型中，β-胺（5）和一些相关的同源物具有抑制血清中催乳素的能力，从而显示出适度的生物学活性。尽管可以认为这些化合物中的吲哚NH相对于乙胺侧链是“元”取向的，但吲哚NH位于另一个“元”位置的化合物（即4- [2-（二-正丙基氨基） ）乙基]吲哚（2）或其刚性苯并[e]吲哚类似物3）是更有效的多巴胺激动剂。结果证明了吲哚NH载体的特定取向。此外，
• NICHOLS, DAVID E.;CASSADY, JOHN M.;PERSONS, PAUL E.;YEUNG, MING C.;CLEMEN+, J. MED. CHEM., 32,(1989) N, C. 2128-2134
  作者：NICHOLS, DAVID E.、CASSADY, JOHN M.、PERSONS, PAUL E.、YEUNG, MING C.、CLEMEN+

  DOI：——

  日期：——
• 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：——
• 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).
• (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.