1-phenylmelatonin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-phenylmelatonin
• 英文别名: N-[2-(5-methoxy-1-phenylindol-3-yl)ethyl]acetamide
• 化学式: C₁₉H₂₀N₂O₂
• 分子量: 308.38
• InChiKey: MHWIVZQVAFEKPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  43.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  碘苯 、 褪黑素 在 4,7-di(pyrrolidin-1-yl)-1,10-phenanthroline 、 potassium hydroxide 、 copper(I) bromide 作用下， 以 水 为溶剂， 反应 21.0h， 以80%的产率得到1-phenylmelatonin
  参考文献：
  名称：

  Selective copper catalysed aromatic N-arylation in water

  摘要：

  4,7-二吡咯烷基-1,10-菲蒽 (DPPhen) 被确定为一种高效的配体，用于在水中催化选择性芳香族氮芳基化的铜催化反应。吲哚、咪唑及嘌呤的氮芳基化反应以中等到优良的产率进行，并对脂肪胺具有完全的选择性。水相介质和低金属及配体用量的可能性使该过程具有良好的环境特征。

  DOI：

  10.1039/c2gc36589h

文献信息

• Acceleration of Pd-Catalyzed Amide N-Arylations Using Cocatalytic Metal Triflates: Substrate Scope and Mechanistic Study
  作者：Joseph Becica、Graham E. Dobereiner

  DOI：10.1021/acscatal.7b01317

  日期：2017.9.1

  comparison with iodobenzene (PhI). The observation of an aryl halide dependence on rate and various qualitative kinetic experiments are consistent with a mechanism in which ligand exchange of halide for amide (“transmetalation”) is turnover limiting. The mechanism may be different depending on whether PhBr or PhI is used as a coupling partner. Oxidative addition complexes (xantphos)Pd(Ph)(X) (X = Br, I;

  助催化三氟甲磺酸金属盐助剂加速了酰胺与芳基卤化物的钯/黄磷催化的交叉偶联。一项对氮亲核试剂的调查显示，当Al（OTf）3时，各种N-芳基酰胺产品的收率都有所提高除了某些例外，它被用作催化添加剂。初始催化速率表明，与溴代碘苯（PhI）相比，使用溴代苯（PhBr）时路易斯酸的加速作用更为明显。芳基卤化物对速率的依赖性以及各种定性动力学实验的观察结果与卤化物配体交换为酰胺（“过渡金属化”）受到限制的机理是一致的。该机制可能会有所不同，具体取决于将PhBr或PhI用作偶联伴侣。制备了氧化加成络合物（xantphos）Pd（Ph）（X）（X = Br，I; xantphos = 4,5-双（二苯基膦基）-9,9-二甲基x吨），可能是催化的中间体; 与Yb（OTf）3的不同相互作用 在溶液中类似于催化机理的卤化物依赖性，我们提出该机理源自催化过程中可逆的路易斯酸介导的卤化物抽象。
• The Copper-Catalyzed <i>N</i>-Arylation of Indoles
  作者：Jon C. Antilla、Artis Klapars、Stephen L. Buchwald

  DOI：10.1021/ja027433h

  日期：2002.10.1

  A general method for the N-arylation of indoles using catalysts derived from Cul and trans-1,2-cyclohexanediamine (1a), trans-N,N'-dimethyl-1,2-cyclohexanediamine (2a), or N,N'-dimethyl-ethylenediamine (3) is reported. N-Arylindoles can be produced in high yield from the coupling of an aryl iodide or aryl bromide with a variety of indoles.
• Melatonin Receptor Ligands:  Synthesis of New Melatonin Derivatives and Comprehensive Comparative Molecular Field Analysis (CoMFA) Study
  作者：Marco Mor、Silvia Rivara、Claudia Silva、Fabrizio Bordi、Pier Vincenzo Plazzi、Gilberto Spadoni、Giuseppe Diamantini、Cesarino Balsamini、Giorgio Tarzia、Franco Fraschini、Valeria Lucini、Romolo Nonno、Bojidar Michaylov Stankov

  DOI：10.1021/jm9810093

  日期：1998.9.1

  The CoMFA methodology was applied to melatonin receptor ligands in order to establish quantitative structure-affinity relationships. One hundred thirty-three compounds were considered: they were either collected from literature or newly synthesized in order to gain information about the less explored positions. To this end, various melatonin derivatives were prepared and their affinity for quail optic tecta melatonin receptor was tested. Compounds were aligned on the putative active conformation of melatonin proposed by our previously reported pharmacophore search, and their relative affinities were calculated from the displacement of 2-[I-125]-iodomelatonin on different tissues expressing aMT receptors. Compounds were grouped into three sets according to their topology. Subset A: melatonin-like compounds; subset B: N-acyl-2-amino-8-methoxytetralins and related compounds; subset C: N-acyl-phenylalkylamines and related compounds. CoMFA models were derived for each set, using the steric, electrostatic, and lipophilic fields as structural descriptors; the PLS analyses were characterized by good statistical parameters, taking into account the heterogeneity of the binding data, obtained with different experimental protocols. From the CoMFA model for the melatonin-like compounds, besides the well-known positive effect of 2-substitution, a low steric tolerance for substituents in 1, 6, and 7, and a negative effect of electron-rich 4-substituents were observed; the information provided by the newly synthesized compounds was essential for these results. Moreover, a comprehensive model for the 133 compounds, accounting for a common alignment and a common mode of interaction at the melatonin receptor, was derived (Q(2) = 0.769, R-2 = 0.905). This model validates our previously reported pharmacophore search and offers a clear depiction of the structure-affinity relationships for the melatonin receptor ligands.
• Receptor-binding studies of 1-N-substituted melatonin analogues
  作者：A Lira-Rocha

  DOI：10.1016/s0223-5234(02)01410-1

  日期：2002.12.1

  In order to analyse the relevance of the indole electronic region in the binding of melatonin to its receptors, we prepared several analogues with p-H, p-NO2, p-MeO, p-F and p-Me of benzyl, benzoyl and phenyl substituents at position 1 of the melatonin skeleton. The electronic properties of the analogues, as calculated with the semiempirical method AM1, were correlated with their affinity for the melatonin receptor from chicken brain membranes. Different trends were observed for each compound series. Compound 5c, with a p-NO2-benzoyl group, showed the best affinity indicating the importance of a polar bulky group in the receptor interaction. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.