N-[3-(2-benzyloxy-5-methoxyphenyl)propyl]propionamide | 1227951-39-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[3-(2-benzyloxy-5-methoxyphenyl)propyl]propionamide
• 英文别名: N-(3-(2-(benzyloxy)-5-methoxyphenyl)propyl)propionamide；N-[3-(5-methoxy-2-phenylmethoxyphenyl)propyl]propanamide
• CAS: 1227951-39-4
• 化学式: C₂₀H₂₅NO₃
• 分子量: 327.423
• InChiKey: VKYABHOVHZOAEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[3-(2-benzyloxy-5-methoxyphenyl)propyl]propionamide 在 copper(l) iodide 、 四(三苯基膦)钯 、 5%-palladium/activated carbon 、 氢气 、 四丁基碘化铵 、 三乙胺 、 三氟乙酸酐 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 N-[3-[5-methoxy-2-[2-(3-methoxyphenyl)ethynyl]phenyl]propyl]propanamide
  参考文献：
  名称：

  Development of substituted N-[3-(3-methoxylphenyl)propyl] amides as MT2-selective melatonin agonists: Improving metabolic stability

  摘要：

  A series of novel and selective N-[3-(6-benzyloxy-3-methoxyphenyl)propyl] amides has recently been shown to possess sub-nanomolar range binding affinity to the type 2 melatonin receptor (MT2). Pharmacokinetics studies suggested that these compounds were subject to vigorous CYP450-mediated metabolism, resulting in a series of metabolites with significantly decreased or diminished binding affinities toward MT2 receptor. The ether bonds were found to be the major positions susceptible to metabolism. In this study, the benzyl ether bond was either removed or replaced with a carbon-carbon bond in an attempt to improve metabolic stability and enhance their resistance towards phase I oxidation. The synthesis, receptor binding affinity, intrinsic potency and metabolic stability of modified structures are reported in this article. By removal or replacement of metabolic labile ether linkerage with carbon linkers, a novel compound was identified with good potency and MT2 selectivity, and with increased metabolic stability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.060
• 作为产物：
  描述：

  3-(2-benzyloxy-5-methoxyphenyl)acrylonitrile 在 锂硼氢 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-[3-(2-benzyloxy-5-methoxyphenyl)propyl]propionamide
  参考文献：
  名称：

  Development of substituted N-[3-(3-methoxylphenyl)propyl] amides as MT2-selective melatonin agonists: Improving metabolic stability

  摘要：

  A series of novel and selective N-[3-(6-benzyloxy-3-methoxyphenyl)propyl] amides has recently been shown to possess sub-nanomolar range binding affinity to the type 2 melatonin receptor (MT2). Pharmacokinetics studies suggested that these compounds were subject to vigorous CYP450-mediated metabolism, resulting in a series of metabolites with significantly decreased or diminished binding affinities toward MT2 receptor. The ether bonds were found to be the major positions susceptible to metabolism. In this study, the benzyl ether bond was either removed or replaced with a carbon-carbon bond in an attempt to improve metabolic stability and enhance their resistance towards phase I oxidation. The synthesis, receptor binding affinity, intrinsic potency and metabolic stability of modified structures are reported in this article. By removal or replacement of metabolic labile ether linkerage with carbon linkers, a novel compound was identified with good potency and MT2 selectivity, and with increased metabolic stability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.060

文献信息

• Synthesis of substituted N-[3-(3-methoxyphenyl)propyl] amides as highly potent MT2-selective melatonin ligands
  作者：Yueqing Hu、Maurice K.C. Ho、King H. Chan、David C. New、Yung H. Wong

  DOI：10.1016/j.bmcl.2010.02.084

  日期：2010.4

  A series of substituted N-[3-(3-methoxyphenyl)propyl]amides were synthesized and their binding affinities towards human melatonin MT1 and MT2 receptors were evaluated. It was discovered that a benzyloxyl substituent incorporated at C6 position of the 3- methoxyphenyl ring dramatically enhanced the MT2 binding affinity and at the same time decreased MT1 binding affinity. (C) 2010 Elsevier Ltd. All rights reserved.
• Development of substituted N-[3-(3-methoxylphenyl)propyl] amides as MT2-selective melatonin agonists: Improving metabolic stability
  作者：Yueqing Hu、Jing Zhu、King H. Chan、Yung H. Wong

  DOI：10.1016/j.bmc.2012.10.060

  日期：2013.1

  A series of novel and selective N-[3-(6-benzyloxy-3-methoxyphenyl)propyl] amides has recently been shown to possess sub-nanomolar range binding affinity to the type 2 melatonin receptor (MT2). Pharmacokinetics studies suggested that these compounds were subject to vigorous CYP450-mediated metabolism, resulting in a series of metabolites with significantly decreased or diminished binding affinities toward MT2 receptor. The ether bonds were found to be the major positions susceptible to metabolism. In this study, the benzyl ether bond was either removed or replaced with a carbon-carbon bond in an attempt to improve metabolic stability and enhance their resistance towards phase I oxidation. The synthesis, receptor binding affinity, intrinsic potency and metabolic stability of modified structures are reported in this article. By removal or replacement of metabolic labile ether linkerage with carbon linkers, a novel compound was identified with good potency and MT2 selectivity, and with increased metabolic stability. (C) 2012 Elsevier Ltd. All rights reserved.