1-(8-Dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indol-1-yl)-2,2,2-trifluoro-ethanone | 165131-96-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-(8-Dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indol-1-yl)-2,2,2-trifluoro-ethanone
• 英文别名: 1-[8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benzo[e]indol-1-yl]-2,2,2-trifluoroethanone
• CAS: 165131-96-4
• 化学式: C₂₀H₂₅F₃N₂O
• 分子量: 366.427
• InChiKey: FNUVHMFBVOHLQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(8-Dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indol-1-yl)-2,2,2-trifluoro-ethanone 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以17%的产率得到Dipropyl-[1-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-yl]-amine
  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：

  6,7,8,9-tetrahydro-N,N-dipropyl-3H-benz[e]indol-8-amine 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 1-(8-Dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indol-1-yl)-2,2,2-trifluoro-ethanone
  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

文献信息

• 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，