N-(2-{7-[(4-methoxybenzyl)amino]naphth-1-yl}ethyl)acetamide | 1096252-78-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(2-{7-[(4-methoxybenzyl)amino]naphth-1-yl}ethyl)acetamide
• 英文别名: N-[2-[7-[(4-methoxyphenyl)methylamino]naphthalen-1-yl]ethyl]acetamide
• CAS: 1096252-78-6
• 化学式: C₂₂H₂₄N₂O₂
• 分子量: 348.445
• InChiKey: WEMZHSQCBPTJHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-{7-[(4-methoxybenzyl)amino]naphth-1-yl}ethyl)acetamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 以62%的产率得到N-[2-(7-amino-naphthalen-1-yl)ethyl]acetamide
  参考文献：
  名称：

  在褪黑激素结合位点MT 3上作为新配体的萘衍生物的设计与合成

  摘要：

  已经合成了MCA-NAT的萘类似物（5-甲氧基羰基氨基-N-乙酰基色胺），并作为褪黑激素受体配体进行了评估。在萘核的C-7位置引入甲氧基羰基氨基取代基产生MT 3选择性配体。可以通过C-7位置和C-1侧链上酰基的适当变化来调节这种选择性。我们鉴定了对MT 3结合位点具有亲和力的新系列化合物，并选择了一个选择性配体（N- [2-（7-甲基氨磺酰基-萘-1-基）乙基]乙酰胺（17，与MT 1和MT相比，Ki为4.9 nM，选择性为1024和20402个受体。

  DOI：

  10.1016/j.ejmech.2011.02.010
• 作为产物：
  描述：

  阿戈美拉汀 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三溴化硼 、 caesium carbonate 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-(2-{7-[(4-methoxybenzyl)amino]naphth-1-yl}ethyl)acetamide
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I)

  摘要：

  As part of our ongoing interest in developing new melatoninergic ligands bearing the same pharmacological profile as agomelatine, we focused our attention on this compound as a lead. Several chemical modifications have been performed on positions C-3 and 8 of the naphthalene ring determined as primary targets for the agomelatine metabolism. Herein we report the modulation of the positions C-3 and 7 in addition of the amide side chain because of this later prominent role in the affinity profile of such ligands. Synthesized compounds were then biologically evaluated at human cloned melatoninergic and serotoninergic receptors and showed different binding affinity and intrinsic activity profiles. Compounds bearing fluoroacetamide group (compounds 4 and 5) showed a high melatoninergic binding affinity particularly towards MT1 receptor subtype. Thus, the fluoroacetamide 4 exhibited a good melatoninergic (mT(1)/MT2) binding affinity (70 pm) higher than the lead. Moreover, other compounds (10a, 10e, 16, 17 and 18) issued from these modulations behaved as MT1 and MT2 agonists and exhibited a sub-nanomolar binding affinity towards these receptors. However, only compounds 10e, 17 and 18 showed a sub-nanomolar binding affinity at 5-HT2C higher than the agomelatine. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.027

文献信息

• Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3
  作者：Véronique Leclerc、Mohamed Ettaoussi、Marouan Rami、Amaury Farce、Jean Albert Boutin、Philippe Delagrange、Daniel-Henri Caignard、Pierre Renard、Pascal Berthelot、Saïd Yous

  DOI：10.1016/j.ejmech.2011.02.010

  日期：2011.5

  no-N-acetyltryptamine) have been synthesized and evaluated as melatonin receptor ligands. Introduction of a methoxycarbonylamino substituent at the C-7 position of the naphthalenic nucleus yields MT3 selective ligands. This selectivity can be modulated with suitable variations of the C-7 position and the acyl group on the C-1 side chain. We identified new series of compounds with affinity for the MT3

  已经合成了MCA-NAT的萘类似物（5-甲氧基羰基氨基-N-乙酰基色胺），并作为褪黑激素受体配体进行了评估。在萘核的C-7位置引入甲氧基羰基氨基取代基产生MT 3选择性配体。可以通过C-7位置和C-1侧链上酰基的适当变化来调节这种选择性。我们鉴定了对MT 3结合位点具有亲和力的新系列化合物，并选择了一个选择性配体（N- [2-（7-甲基氨磺酰基-萘-1-基）乙基]乙酰胺（17，与MT 1和MT相比，Ki为4.9 nM，选择性为1024和20402个受体。
• Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I)
  作者：Mohamed Ettaoussi、Ahmed Sabaouni、Marouan Rami、Jean A. Boutin、Philippe Delagrange、Pierre Renard、Michael Spedding、Daniel-Henri Caignard、Pascal Berthelot、Saïd Yous

  DOI：10.1016/j.ejmech.2012.01.027

  日期：2012.3

  As part of our ongoing interest in developing new melatoninergic ligands bearing the same pharmacological profile as agomelatine, we focused our attention on this compound as a lead. Several chemical modifications have been performed on positions C-3 and 8 of the naphthalene ring determined as primary targets for the agomelatine metabolism. Herein we report the modulation of the positions C-3 and 7 in addition of the amide side chain because of this later prominent role in the affinity profile of such ligands. Synthesized compounds were then biologically evaluated at human cloned melatoninergic and serotoninergic receptors and showed different binding affinity and intrinsic activity profiles. Compounds bearing fluoroacetamide group (compounds 4 and 5) showed a high melatoninergic binding affinity particularly towards MT1 receptor subtype. Thus, the fluoroacetamide 4 exhibited a good melatoninergic (mT(1)/MT2) binding affinity (70 pm) higher than the lead. Moreover, other compounds (10a, 10e, 16, 17 and 18) issued from these modulations behaved as MT1 and MT2 agonists and exhibited a sub-nanomolar binding affinity towards these receptors. However, only compounds 10e, 17 and 18 showed a sub-nanomolar binding affinity at 5-HT2C higher than the agomelatine. (C) 2012 Elsevier Masson SAS. All rights reserved.