N-[(4-methoxy-1H-indol-2-yl)methyl]propionamide | 213682-30-5

• 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-[(4-methoxy-1H-indol-2-yl)methyl]propionamide
• 英文别名: Propanamide, N-[(4-methoxy-1H-indol-2-yl)methyl]；N-[(4-methoxy-1H-indol-2-yl)methyl]propanamide
• CAS: 213682-30-5
• 化学式: C₁₃H₁₆N₂O₂
• 分子量: 232.282
• InChiKey: YWPADYLLRUQSKO-UHFFFAOYSA-N

物化性质

• 熔点：
  117 °C
• 沸点：
  509.9±40.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 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：
  54.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-氯氯苄 、 N-[(4-methoxy-1H-indol-2-yl)methyl]propionamide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 以73%的产率得到N-[1-(4-Chloro-benzyl)-4-methoxy-1H-indol-2-ylmethyl]-propionamide
  参考文献：
  名称：

  2-N-Acylaminoalkylindoles:  Design and Quantitative Structure−Activity Relationship Studies Leading to MT₂-Selective Melatonin Antagonists

  摘要：

  Several indole analogues of melatonin (MLT) were obtained by moving the MLT side chain from C-3 to C-2 of the indole ring. Binding and in vitro functional assays were performed on cloned human MT1 and MT2 receptors, stably transfected in NIH3T3 cells. Quantitative structure-activity relationship studies showed that 4-methoxy-2-(N-acylaminomethyl)indoles, with a benzyl group in position 1, were selective MT2 antagonists and, in particular, N-[(1-p-chlorobenzyl-4-methoxy-1H-indol-2-yl)methyl]propanamide (12) behaved as a pure antagonist at MT1 and MT2 receptors, with a 148-fold selectivity for MT2. We present a topographical model that suggests a lipophilic group, located out of the plane of the indole ring of MLT, as the key feature of the MT2 selective antagonists.

  DOI：

  10.1021/jm001125h
• 作为产物：
  描述：

  4-甲氧吲哚-2-羧酸甲脂 在 氢氧化钾 、 lithium aluminium tetrahydride 、 氯化亚砜 、 氨 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 47.0h， 生成 N-[(4-methoxy-1H-indol-2-yl)methyl]propionamide
  参考文献：
  名称：

  2-[N-Acylamino(C₁−C₃)alkyl]indoles as MT₁ Melatonin Receptor Partial Agonists, Antagonists, and Putative Inverse Agonists

  摘要：

  The synthesis of several novel indole melatonin analogues substituted at the 2-position with acylaminomethyl (8-11), acylaminoethyl (5a-k), or acylaminopropyl (13) side chains is reported. On the basis of a novel in vitro functional assay (specific binding of [S-35]GTP gamma S), which can discriminate agonist from partial agonist, antagonist, and inverse agonist ligands, Ba,g,h,j and 13 were shown to be partial agonists, 5d,e and 8-11 competitive antagonists, and 5b,c,k putative inverse agonists. Binding and functional assays were performed on cloned human MT1 receptor. Structure-activity relationship considerations indicate that N-[1-aryl-2-(4-methoxy-1H-indol-2-yl)(C-1-C-2)alkyl]alkanamides represent a lead structure for this type of ligands.

  DOI：

  10.1021/jm970721h

文献信息

• Analysis of Structure−Activity Relationships for MT₂ Selective Antagonists by Melatonin MT₁ and MT₂ Receptor Models
  作者：Silvia Rivara、Simone Lorenzi、Marco Mor、Pier Vincenzo Plazzi、Gilberto Spadoni、Annalida Bedini、Giorgio Tarzia

  DOI：10.1021/jm048956y

  日期：2005.6.1

  Three-dimensional homology models of human MT1 and MT2 melatonin receptors were built with the aim to investigate the structure-activity relationships (SARs) of MT2 selective antagonists. A common interaction pattern was proposed for a series of structurally different MT2 selective antagonists, which were positioned within the binding site by docking and simulated annealing. The proposed antagonist binding mode to the MT2 receptor is characterized by the accommodation of the out-of-plane substituents in a hydrophobic pocket, which resulted as being fundamental for the explanation of the antagonist behavior and the MT2 receptor selectivity. Moreover, to assess the ability of the MT2 receptor model to reproduce the SARs of MT2 antagonists, three new derivatives of the MT2 selective antagonist N-[1-(4-chloro-benzyl)-4-methoxy-1H-indol-2-ylmethyl]-propionamide (7) were synthesized and tested for their receptor affinity and intrinsic activity. These compounds were docked into the MT2 receptor model and were submitted to molecular dynamics studies, providing results in qualitative agreement with the experimental data. These results confirm the importance of the out-of-plane group in receptor binding and selectivity and provide a partial validation of the proposed G protein-coupled receptor model.
• [EN] USE OF ANTIOXIDANTS TO TREAT BONE LOSS DISORDERS<br/>[FR] UTILISATION D'ANTIOXYDANTS POUR TRAITER LES TROUBLES ASSOCIES A LA PERTE OSSEUSE
  申请人：ST GEORGES ENTPR LTD

  公开号：WO2004093995A2

  公开（公告）日：2004-11-04

  Bone loss disorders can be treated or prevented by administration of an agent which increases the levels of oxidant defences and/or at least one antioxidant in a subject. The agent can be an antioxidant and may act either directly to increase antioxidant levels and/or oxidant defences or indirectly.
• 2-<i>N</i>-Acylaminoalkylindoles:  Design and Quantitative Structure−Activity Relationship Studies Leading to MT₂-Selective Melatonin Antagonists
  作者：Gilberto Spadoni、Cesarino Balsamini、Giuseppe Diamantini、Andrea Tontini、Giorgio Tarzia、Marco Mor、Silvia Rivara、Pier Vincenzo Plazzi、Romolo Nonno、Valeria Lucini、Marilou Pannacci、Franco Fraschini、Bojidar Michaylov Stankov

  DOI：10.1021/jm001125h

  日期：2001.8.1

  Several indole analogues of melatonin (MLT) were obtained by moving the MLT side chain from C-3 to C-2 of the indole ring. Binding and in vitro functional assays were performed on cloned human MT1 and MT2 receptors, stably transfected in NIH3T3 cells. Quantitative structure-activity relationship studies showed that 4-methoxy-2-(N-acylaminomethyl)indoles, with a benzyl group in position 1, were selective MT2 antagonists and, in particular, N-[(1-p-chlorobenzyl-4-methoxy-1H-indol-2-yl)methyl]propanamide (12) behaved as a pure antagonist at MT1 and MT2 receptors, with a 148-fold selectivity for MT2. We present a topographical model that suggests a lipophilic group, located out of the plane of the indole ring of MLT, as the key feature of the MT2 selective antagonists.
• 2-[<i>N</i>-Acylamino(C₁−C₃)alkyl]indoles as MT₁ Melatonin Receptor Partial Agonists, Antagonists, and Putative Inverse Agonists
  作者：Gilberto Spadoni、Cesarino Balsamini、Annalida Bedini、Giuseppe Diamantini、Barbara Di Giacomo、Andrea Tontini、Giorgio Tarzia、Marco Mor、Pier Vincenzo Plazzi、Silvia Rivara、Romolo Nonno、Marilou Pannacci、Valeria Lucini、Franco Fraschini、Bojidar Michaylov Stankov

  DOI：10.1021/jm970721h

  日期：1998.9.1

  The synthesis of several novel indole melatonin analogues substituted at the 2-position with acylaminomethyl (8-11), acylaminoethyl (5a-k), or acylaminopropyl (13) side chains is reported. On the basis of a novel in vitro functional assay (specific binding of [S-35]GTP gamma S), which can discriminate agonist from partial agonist, antagonist, and inverse agonist ligands, Ba,g,h,j and 13 were shown to be partial agonists, 5d,e and 8-11 competitive antagonists, and 5b,c,k putative inverse agonists. Binding and functional assays were performed on cloned human MT1 receptor. Structure-activity relationship considerations indicate that N-[1-aryl-2-(4-methoxy-1H-indol-2-yl)(C-1-C-2)alkyl]alkanamides represent a lead structure for this type of ligands.