6-bromo-N10-methyl-N10-Boc-tryptamine | 209168-89-8

• 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: 6-bromo-N10-methyl-N10-Boc-tryptamine
• 英文别名: 1,1-Dimethylethyl N-[2-(6-bromo-1H-indol-3-yl)ethyl]-N-methylcarbamate；tert-butyl N-[2-(6-bromo-1H-indol-3-yl)ethyl]-N-methylcarbamate
• CAS: 209168-89-8
• 化学式: C₁₆H₂₁BrN₂O₂
• 分子量: 353.259
• InChiKey: VHPHCKKJZZGQDI-UHFFFAOYSA-N

物化性质

• 熔点：
  120-124 °C
• 沸点：
  468.5±33.0 °C(Predicted)
• 密度：
  1.355±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-N10-methyl-N10-Boc-tryptamine 在 次氯酸叔丁酯 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2-[6-溴-2-(2-甲基-3-丁烯-2-基)-1H-吲哚-3-基]-N-甲基乙胺盐酸盐(1:1)
  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：

  6-溴吲哚 在 三乙胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-bromo-N10-methyl-N10-Boc-tryptamine
  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

• Synthesis of the brominated marine alkaloids (±)-arborescidine A, B and C
  作者：Brigitte E.A. Burm、Michaël M. Meijler、Jacco Korver、Martin J. Wanner、Gerrit-Jan Koomen

  DOI：10.1016/s0040-4020(98)00306-8

  日期：1998.5

  brominated marine alkaloids arborescidine A (1), B (2) and C (3), starting from 6-bromo-(N-methyl) trypatamine is described. An equilibrium, under both basic and acidic conditions was found to exist between the trans- and cis-isomers 3 and 4. Spectral data indicated that the structure of isomer 4 does not correspond with the compound identified as arborescidine D recently isolated from the marine tunicate

  描述了从6-溴-（N-甲基）色胺的直接合成溴化海洋生物碱阿糖胞苷A（1），B（2）和C（3）的方法。的平衡，碱性和酸性条件下被发现之间存在反式-和顺式-异构体3和4。光谱数据表明，异构体4的结构与最近从海洋被膜植物假单胞菌假单胞菌中分离出的鉴定为阿糖胞苷D的化合物不符。
• Synthesis and evaluation of N1-alkylindole-3-ylalkylammonium compounds as nicotinic acetylcholine receptor ligands
  作者：Edwin G. Pérez、Bruce K. Cassels、Christoph Eibl、Daniela Gündisch

  DOI：10.1016/j.bmc.2012.04.050

  日期：2012.6

  In this study thirty-three novel indole derivatives were designed and synthesized based on the structure of deformylflustrabromine B (1), a metabolite isolated from the marine bryozoan Flustra foliacea L. The syntheses were carried out using standard methodologies and in good yields. The molecules were tested for their affinities for the alpha 4 beta 2*, alpha 3 beta 4*, alpha 7* and (alpha 1)(2)beta 1 gamma delta nicotinic acetylcholine receptor (nAChR) sub-types. Binding assays showed that, among these ligands, compound 7c exhibited the highest affinity with K-i = 136.1, 93.9 and 862.4 nM for the alpha 4 beta 2*, alpha 3 beta 4*, and alpha 7* nAChRs subtypes, respectively. These results indicated that the indole core might be a useful scaffold for the development of new potent and selective nAChR ligands. (C) 2012 Elsevier Ltd. All rights reserved.
• 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.
• Deconstruction of the α4β2 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator Desformylflustrabromine
  作者：Nadezhda German、Jin-Sung Kim、Atul Jain、Malgorzata Dukat、Anshul Pandya、Yilong Ma、Maegan Weltzin、Marvin K. Schulte、Richard A. Glennon

  DOI：10.1021/jm200834x

  日期：2011.10.27

  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.