3-(2-((trimethylsilyl)oxy)ethyl)-1H-indole | 691880-05-4

• 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-(2-((trimethylsilyl)oxy)ethyl)-1H-indole
• 英文别名: Trimethyl[2-(1H-indole-3-yl)ethoxy]silane；2-(1H-indol-3-yl)ethoxy-trimethylsilane
• CAS: 691880-05-4
• 化学式: C₁₃H₁₉NOSi
• 分子量: 233.385
• InChiKey: POFKQPYUTWBSJV-UHFFFAOYSA-N

物化性质

• 沸点：
  329.6±25.0 °C(Predicted)
• 密度：
  1.031±0.06 g/cm3(Predicted)
• 保留指数：
  1843.2

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  25
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(2-((trimethylsilyl)oxy)ethyl)-1H-indole 在 三甲基氯硅烷 、 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 、 丁酮 为溶剂， 反应 18.0h， 生成 trans-4',9'-dihydro-N,N-dimethyl-4-phenyl-3'H-spiro[cyclohexane-1,1'-pyrano[3,4-b]indol]-4-amine hydrochloride
  参考文献：
  名称：

  Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol

  摘要：

  In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

  DOI：

  10.1021/ml500117c
• 作为产物：
  描述：

  三甲基氯硅烷 、 色醇 在 咪唑 作用下， 生成 3-(2-((trimethylsilyl)oxy)ethyl)-1H-indole
  参考文献：
  名称：

  基于四唑的生长激素促分泌剂的发现，合成和结构活性研究。

  摘要：

  基于四唑模板，发现了一类新型的生长激素促分泌素（GHS）。描述了这种新型GHS中的体外SAR和体内效价。四唑9q在大鼠和狗中表现出良好的口服生物利用度，以及在狗中口服10 mg / kg剂量后的功效。已经开发了用于合成基于四唑的GHS的溶液和固相方案。

  DOI：

  10.1016/j.bmcl.2007.07.099

文献信息

• Discovery, synthesis, and structure–activity studies of tetrazole based growth hormone secretagogues
  作者：Andrés S. Hernández、Peter T.W. Cheng、Christa M. Musial、Stephen G. Swartz、Rocco J. George、Gary Grover、Dorothy Slusarchyk、R. Krishna Seethala、Mark Smith、Kenneth Dickinson、Leah Giupponi、Daniel A. Longhi、Neil Flynn、Brian J. Murphy、David A. Gordon、Scott A. Biller、Jeffrey A. Robl、Joseph A. Tino

  DOI：10.1016/j.bmcl.2007.07.099

  日期：2007.11

  Growth Hormone Secretagogues (GHS), based on a tetrazole template, has been discovered. In vitro SAR and in vivo potency within this new class of GHS are described. The tetrazole 9q exhibits good oral bioavailability in rats and dogs as well as efficacy following an oral 10 mg/kg dose in dogs. Solution and solid phase protocols for the synthesis of tetrazole based GHS have been developed.

  基于四唑模板，发现了一类新型的生长激素促分泌素（GHS）。描述了这种新型GHS中的体外SAR和体内效价。四唑9q在大鼠和狗中表现出良好的口服生物利用度，以及在狗中口服10 mg / kg剂量后的功效。已经开发了用于合成基于四唑的GHS的溶液和固相方案。
• [DE] SPIROCYCLISCHE CYCLOHEXAN-DERIVATE<br/>[EN] SPIROCYCLIC CYCLOHEXANE DERIVATIVES<br/>[FR] DERIVES DE CYCLOHEXANE SPIROCYCLIQUES
  申请人：GRUENENTHAL GMBH

  公开号：WO2004043967A1

  公开（公告）日：2004-05-27

  Die vorliegende Erfindung betrifft spirocyclische Cyclohexan-Drerivate, Verfahren zu deren Herstellung, Arzneimittel enthaltend diese Verbindungen und die Verwendung von spirocyclischen Cyclohexan-Derivaten zur Herstellung von Arzneimitteln.

  这项发明涉及螺环状环己烷衍生物，其制备方法，包含这些化合物的药物以及使用螺环状环己烷衍生物制备药物的用途。
• Discovery of Spiro[cyclohexane-dihydropyrano[3,4-<i>b</i>]indole]-amines as Potent NOP and Opioid Receptor Agonists
  作者：Stefan Schunk、Klaus Linz、Sven Frormann、Claudia Hinze、Stefan Oberbörsch、Bernd Sundermann、Saskia Zemolka、Werner Englberger、Tieno Germann、Thomas Christoph、Babette-Y. Kögel、Wolfgang Schröder、Stephanie Harlfinger、Derek Saunders、Achim Kless、Hans Schick、Helmut Sonnenschein

  DOI：10.1021/ml500116x

  日期：2014.8.14

  We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors.
• Catalytic Friedel–Crafts Reaction of Aminocyclopropanes
  作者：Florian de Nanteuil、Joachim Loup、Jérôme Waser

  DOI：10.1021/ol401616a

  日期：2013.7.19

  A Lewis acid catalyzed Friedel-Crafts reaction between donor-acceptor aminocyclopropanes and indoles and other electron-rich aromatic compounds is reported. Indole alkylation at the C3 position was generally obtained for a broad range of functional groups and substitution patterns. In the case of C3-substituted indoles, C2 alkylation was observed. The reaction gives a rapid access to gamma amino acid derivatives present in numerous bioactive molecules.
• Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol
  作者：Stefan Schunk、Klaus Linz、Claudia Hinze、Sven Frormann、Stefan Oberbörsch、Bernd Sundermann、Saskia Zemolka、Werner Englberger、Tieno Germann、Thomas Christoph、Babette-Y. Kögel、Wolfgang Schröder、Stephanie Harlfinger、Derek Saunders、Achim Kless、Hans Schick、Helmut Sonnenschein

  DOI：10.1021/ml500117c

  日期：2014.8.14

  In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.