N-[2-(3-fluoromethyl-7-methoxy-naphthalen-1-yl)ethyl]acetamide | 1363155-86-5

• 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-(3-fluoromethyl-7-methoxy-naphthalen-1-yl)ethyl]acetamide
• 英文别名: N-[2-[3-(fluoromethyl)-7-methoxynaphthalen-1-yl]ethyl]acetamide
• CAS: 1363155-86-5
• 化学式: C₁₆H₁₈FNO₂
• 分子量: 275.323
• InChiKey: BKRSGUOHAVKIQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  阿戈美拉汀 在 aluminum (III) chloride 、 sodium hypochlorite 、 lithium aluminium tetrahydride 、 氯化亚砜 、 二乙胺基三氟化硫 、 水 、 potassium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-[2-(3-fluoromethyl-7-methoxy-naphthalen-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