tert-butyl (2-(6-bromo-2-(2-methylbut-3-en-2-yl)-1H-indol-3-yl)ethyl)(methyl)carbamate | 951322-09-1

• 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: tert-butyl (2-(6-bromo-2-(2-methylbut-3-en-2-yl)-1H-indol-3-yl)ethyl)(methyl)carbamate
• 英文别名: tert-butyl 2-(6-bromo-2-(1,1-dimethylallyl)-1H-indol-3-yl)ethyl-N-methylcarbamate
• CAS: 951322-09-1
• 化学式: C₂₁H₂₉BrN₂O₂
• 分子量: 421.377
• InChiKey: CBYAHGUPGYBPJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  45.33
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-(6-bromo-2-(2-methylbut-3-en-2-yl)-1H-indol-3-yl)ethyl)(methyl)carbamate 在 sodium tetrahydroborate 、 cobalt(II) chloride hexahydrate 作用下， 以 乙醇 为溶剂， 以76%的产率得到tert-butyl N-[2-[6-bromo-2-(2-methylbutan-2-yl)-1H-indol-3-yl]ethyl]-N-methylcarbamate
  参考文献：
  名称：

  Deconstruction of the α4β2 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator Desformylflustrabromine

  摘要：

  Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of alpha 4 beta 2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techniques. Although the intact structure of 1 was found to be optimal, several deconstructed analogs retained activity. Neither the 6-bromo substituent nor the entire 2-position chain is required for activity. In particular, reduction of the olefinic side chain of 1, as seen with 6, not only resulted in retention of activity/potency but in enhanced selectivity for alpha 4 beta 2 versus alpha 7 nACh receptors. Pharmacophoric features for the allosteric modulation of alpha 4 beta 2 nACh receptors by 1 were identified.

  DOI：

  10.1021/jm200834x
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 次氯酸叔丁酯 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (2-(6-bromo-2-(2-methylbut-3-en-2-yl)-1H-indol-3-yl)ethyl)(methyl)carbamate
  参考文献：
  名称：

  Deconstruction of the α4β2 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator Desformylflustrabromine

  摘要：

  Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of alpha 4 beta 2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techniques. Although the intact structure of 1 was found to be optimal, several deconstructed analogs retained activity. Neither the 6-bromo substituent nor the entire 2-position chain is required for activity. In particular, reduction of the olefinic side chain of 1, as seen with 6, not only resulted in retention of activity/potency but in enhanced selectivity for alpha 4 beta 2 versus alpha 7 nACh receptors. Pharmacophoric features for the allosteric modulation of alpha 4 beta 2 nACh receptors by 1 were identified.

  DOI：

  10.1021/jm200834x

文献信息

• <i>des</i>-Formylflustrabromine (dFBr): A Structure–Activity Study on Its Ability To Potentiate the Action of Acetylcholine at α4β2 Nicotinic Acetylcholine Receptors
  作者：Małgorzata Dukat、Atul Jain、Nadezhda German、Rossana Ferrara-Pontoriero、Yanzhou Huang、Yilong Ma、Marvin K. Schulte、Richard A. Glennon

  DOI：10.1021/acschemneuro.8b00156

  日期：2018.12.19

  modulator (PAM) at α4β2 nicotinic acetylcholine receptors (nAChRs). We previously deconstructed this agent to determine which of its structural features contribute to its actions and have identified an agent that might serve as the basis for a " working pharmacophore". Here, we elaborate the dFBr (1; EC50 = 0.2 μM) structure to identify how various structural modifications impact its actions. Electrophysiological

  天然吲哚生物碱去甲酰基氟乙溴（dFBr; 1）是最早被证明对α4β2烟碱乙酰胆碱受体（nAChRs）具有选择性正变构调节剂（PAM）的药物之一。我们以前对这种药物进行了解构，以确定其结构特征中的哪些有助于其作用，并确定了可能用作“有效药效基团”基础的药物。在这里，我们详细阐述了dFBr（1; EC50 = 0.2μM）结构，以确定各种结构修饰如何影响其作用。非洲爪蟾卵母细胞的电生理研究确定了几种具有dFBr样效力的化合物，一种化合物是5溴类似物1（即5-溴dFBr； 25； EC50 = 0.4μM），其功效是1的5倍以上。在α4β2nAChRs处的PAM。
• Synthesis of desformylflustrabromine and its evaluation as an α4β2 and α7 nACh receptor modulator
  作者：Jin-Sung Kim、Anshul Padnya、Maegan Weltzin、Brian W. Edmonds、Marvin K. Schulte、Richard A. Glennon

  DOI：10.1016/j.bmcl.2007.06.047

  日期：2007.9

  Desformylflustrabromine (dFBr; 1) and desformylflustrabromine-B (dFBr-B; 2) have been previously isolated from natural sources, and the former has been demonstrated to be a novel and selective positive allosteric modulator of alpha 4 beta 2 nicotinic acetylcholine (nACh) receptors. The present study describes the synthesis of water-soluble salts of I and 2, and confirms and further investigates the actions of I and 2 using two-electrode voltage clamp recordings. (C) 2007 Elsevier Ltd. All rights reserved.