3-(4-iodobutyl)-1H-indole-5-carbonitrile | 692756-88-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(4-iodobutyl)-1H-indole-5-carbonitrile
• 英文别名: 3-(4-iodo-butyl)-1H-indole-5-carbonitrile；1H-Indole-5-carbonitrile, 3-(4-iodobutyl)-
• CAS: 692756-88-0
• 化学式: C₁₃H₁₃IN₂
• 分子量: 324.164
• InChiKey: RAEJZFCFZAHVMP-UHFFFAOYSA-N

物化性质

• 熔点：
  117-119 °C(Solv: hexane (110-54-3); ethyl ether (60-29-7))
• 沸点：
  468.2±35.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  39.6
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(4-iodobutyl)-1H-indole-5-carbonitrile 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 水 为溶剂， 反应 75.0h， 生成
  参考文献：
  名称：

  Dual 5-HT1A agonists and 5-HT re-uptake inhibitors by combination of indole-butyl-amine and chromenonyl-piperazine structural elements in a single molecular entity

  摘要：

  The dual serotonin (5-HT) re-uptake inhibitor and 5-HT1A receptor agonist vilazodone was found to increase central serotonin levels in rat brain. In the course of structural modifications of vilazodone 3-{4-[4-(2-oxo-2H-1-benzopyran-6-yl)-1-piperazinyl]-butyl}-1H-indole-5-carbonitrile 8i and its fluorine analogue 6-{4-[4-(5-fluor-3-indolyl)-butyl]-1-piperazinyl}-2H-1-benzopyran-2-one have been identified. These unsubstituted chromenones are equally potent at the 5-HT1A receptor and 5-HT transporter. The implementation of nitrogen functionalities in position 3 of the chromenones resulted in compounds acting as agonists at the 5-HT1A receptor and as 5-HT re-uptake inhibitors like vilazodone. Ex vivo 5-HT re-uptake inhibition and in vitro 5-HT agonism were determined in the PCA- and GTRgammaS-assay, respectively. The potential of these chromenones to increase central 5-HT levels was measured in microdialysis studies and especially the derivatives 3-{4-[4-(3-amino-2-oxo-2H-chromen-6-yl)-piperazin-1-yl]-butyl-1H-indole-5-carbonitrile 8f, ethyl (6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-carbamate 8h and N-(6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-acetamide 8k give rise to rapid development of increased serotonin levels in rat brain cortex, lasting longer than 3h. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.014
• 作为产物：
  描述：

  3-(4-chlorobutyl)-1H-indole-5-carbonitrile 在 sodium iodide 作用下， 以 丙酮 为溶剂， 以88%的产率得到3-(4-iodobutyl)-1H-indole-5-carbonitrile
  参考文献：
  名称：

  Dual 5-HT1A agonists and 5-HT re-uptake inhibitors by combination of indole-butyl-amine and chromenonyl-piperazine structural elements in a single molecular entity

  摘要：

  The dual serotonin (5-HT) re-uptake inhibitor and 5-HT1A receptor agonist vilazodone was found to increase central serotonin levels in rat brain. In the course of structural modifications of vilazodone 3-{4-[4-(2-oxo-2H-1-benzopyran-6-yl)-1-piperazinyl]-butyl}-1H-indole-5-carbonitrile 8i and its fluorine analogue 6-{4-[4-(5-fluor-3-indolyl)-butyl]-1-piperazinyl}-2H-1-benzopyran-2-one have been identified. These unsubstituted chromenones are equally potent at the 5-HT1A receptor and 5-HT transporter. The implementation of nitrogen functionalities in position 3 of the chromenones resulted in compounds acting as agonists at the 5-HT1A receptor and as 5-HT re-uptake inhibitors like vilazodone. Ex vivo 5-HT re-uptake inhibition and in vitro 5-HT agonism were determined in the PCA- and GTRgammaS-assay, respectively. The potential of these chromenones to increase central 5-HT levels was measured in microdialysis studies and especially the derivatives 3-{4-[4-(3-amino-2-oxo-2H-chromen-6-yl)-piperazin-1-yl]-butyl-1H-indole-5-carbonitrile 8f, ethyl (6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-carbamate 8h and N-(6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-acetamide 8k give rise to rapid development of increased serotonin levels in rat brain cortex, lasting longer than 3h. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.014

文献信息

• [DE] CHROMENONINDOLE<br/>[EN] CHROMENONE INDOLES<br/>[FR] CHROMENONINDOLE
  申请人：MERCK PATENT GMBH

  公开号：WO2004087692A1

  公开（公告）日：2004-10-14

  Chromenonindol-Derivate der Formel (I) worin R1, R2, R3, R, A und B die in Anspruch 1 angegebenen Bedeutungen besitzen, sowie deren pharmazeutisch verwendbaren Prodrugs, Derivate, Solvate, Stereoisomere und Salze zeigen besondere Wirkungen auf das Zentralnervensystem, vor allem 5 HT-Wiederaufnahme hemmende und 5 HTx-agonistische und/oder-antagonistische Wirkungen. Sie zeichnen sich durch eine besonders hohe Bioverfügbarkeit und eine besonders hohe Hemmung der 5 HT-Wiederaufnahme aus.

  Chromenonindol-Derivate der Formel (I)，其中R1、R2、R3、R、A和B具有权利要求1中所述的含义，以及它们的药用可用前药、衍生物、溶剂化合物、立体异构体和盐对中枢神经系统表现出特殊作用，尤其是5-HT再摄取抑制和5-HTx激动和/或拮抗作用。它们具有特别高的生物利用度和对5-HT再摄取的特别高抑制作用。
• [DE] INDOLDERIVATE MIT 5HT1A AFFINITÄT<br/>[EN] INDOLE DERIVATIVE WITH 5HT1A AFFINITY<br/>[FR] DERIVES D'INDOLE PRESENTANT UNE AFFINITE VIS-A-VIS DE LA 5HT1A
  申请人：MERCK PATENT GMBH

  公开号：WO2004041815A1

  公开（公告）日：2004-05-21

  Neue Indolderivate der Formel (I), worin A , X, R1, R1’ und m die in Patentanspruch 1 angegebenen Bedeutungen haben, weisen sie eine starke Affinität zu den 5-HT1A- und teilweise zu den 5-HT1D- Rezeptoren auf. Die Verbindungen hemmen die Serotonin-Wiederaufnahme, zeigen serotonin-agonistische und -antagonistische Eigenschaften und eignen sich als Antidepressiva, Anxiolytika und zur Behandlung neurodegenerativer Erkrankungen.

  新的Indolderivate的化学式为（I），其中A，X，R1，R1'和m的含义如专利权要求书1所述，它们具有对5-HT1A和部分5-HT1D受体的强烈亲和力。这些化合物抑制了血清素的再摄取，表现出血清素激动剂和拮抗剂的特性，并适用于抗抑郁剂、抗焦虑剂和治疗神经退行性疾病。
• CHROMENONINDOLE
  申请人：Merck Patent GmbH

  公开号：EP1611126B1

  公开（公告）日：2009-10-28
• US7968551B2
  申请人：——

  公开号：US7968551B2

  公开（公告）日：2011-06-28