N,N-di-n-hexyl-[2-(4-nitrophenyl)indol-3-yl]glyoxylamide | 1060748-36-8

• 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: N,N-di-n-hexyl-[2-(4-nitrophenyl)indol-3-yl]glyoxylamide
• 英文别名: N,N-dihexyl-2-(2-(4-nitrophenyl)-1H-indol-3-yl)-2-oxoacetamide；N,N-dihexyl-2-[2-(4-nitrophenyl)-1H-indol-3-yl]-2-oxoacetamide
• CAS: 1060748-36-8
• 化学式: C₂₈H₃₅N₃O₄
• 分子量: 477.604
• InChiKey: XUNMBICMEBGIRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-di-n-hexyl-[2-(4-nitrophenyl)indol-3-yl]glyoxylamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 以68%的产率得到2-[2-(4-aminophenyl)-1H-indol-3-yl]-N,N-dihexyl-2-oxoacetamide
  参考文献：
  名称：

  Deepening the Topology of the Translocator Protein Binding Site by Novel N,N-Dialkyl-2-arylindol-3-ylglyoxylamides

  摘要：

  As a continuation of our studies on 2-phenylindol-3-ylglyoxylamides as potent and selective translocator protein (TSPO) ligands, two subsets of novel derivatives, featuring hydrophilic group (OH, NH2, COOH) at the para-position of the pendent 2-phenyl ring (8-16) or different 2-aryl moieties, namely, 3-thienyl, p-biphenyl, 2-naphthyl (23-35), were synthesized and biologically evaluated, some of them showing K-i values in the subnanomolar range and the 2-naphthyl group performance being the best. The resulting SARs confirmed the key role played by interactions taking place between ligands and the lipophilic Li pocket of the TSPO binding site. Docking simulations were performed on the most potent compound of the present series (29) exploiting the recently available 3D structures of TSPO bound to its standard ligand (PK11195). Our theoretical model was fully consistent with SARs of the newly investigated as well of the previously reported 2-phenylindol-3-ylglyoxylamide derivatives.

  DOI：

  10.1021/acs.jmedchem.5b00689
• 作为产物：
  描述：

  2-(4-nitrophenyl)-1H-indole 在 三乙胺 作用下， 以 乙醚 、 甲苯 为溶剂， 生成 N,N-di-n-hexyl-[2-(4-nitrophenyl)indol-3-yl]glyoxylamide
  参考文献：
  名称：

  Deepening the Topology of the Translocator Protein Binding Site by Novel N,N-Dialkyl-2-arylindol-3-ylglyoxylamides

  摘要：

  As a continuation of our studies on 2-phenylindol-3-ylglyoxylamides as potent and selective translocator protein (TSPO) ligands, two subsets of novel derivatives, featuring hydrophilic group (OH, NH2, COOH) at the para-position of the pendent 2-phenyl ring (8-16) or different 2-aryl moieties, namely, 3-thienyl, p-biphenyl, 2-naphthyl (23-35), were synthesized and biologically evaluated, some of them showing K-i values in the subnanomolar range and the 2-naphthyl group performance being the best. The resulting SARs confirmed the key role played by interactions taking place between ligands and the lipophilic Li pocket of the TSPO binding site. Docking simulations were performed on the most potent compound of the present series (29) exploiting the recently available 3D structures of TSPO bound to its standard ligand (PK11195). Our theoretical model was fully consistent with SARs of the newly investigated as well of the previously reported 2-phenylindol-3-ylglyoxylamide derivatives.

  DOI：

  10.1021/acs.jmedchem.5b00689

文献信息

• Anxiolytic-like Effects of <i>N</i>,<i>N</i>-Dialkyl-2-phenylindol-3-ylglyoxylamides by Modulation of Translocator Protein Promoting Neurosteroid Biosynthesis
  作者：Federico Da Settimo、Francesca Simorini、Sabrina Taliani、Concettina La Motta、Anna Maria Marini、Silvia Salerno、Marusca Bellandi、Ettore Novellino、Giovanni Greco、Barbara Cosimelli、Eleonora Da Pozzo、Barbara Costa、Nicola Simola、Micaela Morelli、Claudia Martini

  DOI：10.1021/jm8003224

  日期：2008.9.25

  Novel N,N-disubstituted indol-3-ylglyoxylamides (1-56), bearing different combinations of substituents R-1-R-5, were synthesized and evaluated as ligands of the translocator protein (TSPO), the 18 kDa protein representing the minimal functional unit of the "peripheral-type benzodiazepine receptor" (PBR). Most of the new compounds showed a nanomolar/subnanomolar affinity for TSPO and stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to or higher than that of classic TSPO ligands such as PK 11195. Moreover, when evaluated in vivo by means of the elevated-plus-maze (EPM) paradigm in the rat, compound 32. the best-performing derivative in terms of TSPO affinity and pregnenolone production, showed clear anxiolytic effects. The results of this study suggested that the novel N, N-di substituted indol-3y1glyoxylani ides may represent a promising class of compounds potentially suited for the treatment of anxiety disorders.
• Deepening the Topology of the Translocator Protein Binding Site by Novel <i>N</i>,<i>N</i>-Dialkyl-2-arylindol-3-ylglyoxylamides
  作者：Elisabetta Barresi、Agostino Bruno、Sabrina Taliani、Sandro Cosconati、Eleonora Da Pozzo、Silvia Salerno、Francesca Simorini、Simona Daniele、Chiara Giacomelli、Anna Maria Marini、Concettina La Motta、Luciana Marinelli、Barbara Cosimelli、Ettore Novellino、Giovanni Greco、Federico Da Settimo、Claudia Martini

  DOI：10.1021/acs.jmedchem.5b00689

  日期：2015.8.13

  As a continuation of our studies on 2-phenylindol-3-ylglyoxylamides as potent and selective translocator protein (TSPO) ligands, two subsets of novel derivatives, featuring hydrophilic group (OH, NH2, COOH) at the para-position of the pendent 2-phenyl ring (8-16) or different 2-aryl moieties, namely, 3-thienyl, p-biphenyl, 2-naphthyl (23-35), were synthesized and biologically evaluated, some of them showing K-i values in the subnanomolar range and the 2-naphthyl group performance being the best. The resulting SARs confirmed the key role played by interactions taking place between ligands and the lipophilic Li pocket of the TSPO binding site. Docking simulations were performed on the most potent compound of the present series (29) exploiting the recently available 3D structures of TSPO bound to its standard ligand (PK11195). Our theoretical model was fully consistent with SARs of the newly investigated as well of the previously reported 2-phenylindol-3-ylglyoxylamide derivatives.