N-[3-[5-methoxy-2-(3-methoxyphenyl)phenyl]propyl]propanamide | 1417544-02-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3-[5-methoxy-2-(3-methoxyphenyl)phenyl]propyl]propanamide
• CAS: 1417544-02-5
• 化学式: C₂₀H₂₅NO₃
• 分子量: 327.423
• InChiKey: ZNOFYIUJRHQQNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  8
• 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-[5-methoxy-2-(3-methoxyphenyl)phenyl]propyl]propanamide 在 tri-n-butylamine pyrophosphate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  自动平行合成5'-三磷酸寡核苷酸和化学修饰的5'-三磷酸小干扰RNA的制备

  摘要：

  描述了用于5'-三磷酸和5'-二磷酸寡核苷酸的平行和高通量固相合成的全自动化学方法。首先使用标准的自动化DNA / RNA固相合成程序构建所需的全长寡核苷酸。然后，在相同的色谱柱和仪器上，不间断的连续循环的有效实施提供了相应的未修饰或化学修饰的5'-三磷酸酯和5'-二磷酸酯。该方法可轻松转换为可扩展的高通量合成方案，与目前的DNA / RNA合成仪兼容，可产生多种独特的5'-多磷酸化寡核苷酸。使用这种方法，我们完成了化学修饰的5'-三磷酸寡核苷酸的合成，将其退火以形成小干扰RNA（ppp-siRNA），这是一类可能令人感兴趣的新型RNAi治疗工具。5'-三磷酸基团附着到siRNA构建体的过客链上，不会引起体外RNAi介导的基因沉默活性的显着改善，也不会引起强烈的特异性体外RIG-I激活。报道的方法将能够筛选许多经过化学修饰的ppp-siRNA，从而产生新型的双功能RNAi治疗平台。5'-三

  DOI：

  10.1016/j.bmc.2012.11.043
• 作为产物：
  描述：

  N-[3-(2-benzyloxy-5-methoxyphenyl)propyl]propionamide 在 四(三苯基膦)钯 、 5%-palladium/activated carbon 、 氢气 、 sodium carbonate 、 三乙胺 、 三氟乙酸酐 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 27.0h， 生成 N-[3-[5-methoxy-2-(3-methoxyphenyl)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

文献信息

• Automated parallel synthesis of 5′-triphosphate oligonucleotides and preparation of chemically modified 5′-triphosphate small interfering RNA
  作者：Ivan Zlatev、Jeremy G. Lackey、Ligang Zhang、Amy Dell、Kathy McRae、Sarfraz Shaikh、Richard G. Duncan、Kallanthottathil G. Rajeev、Muthiah Manoharan

  DOI：10.1016/j.bmc.2012.11.043

  日期：2013.2

  5′-triphosphates and 5′-diphosphates. The method was readily translated into a scalable and high-throughput synthesis protocol compatible with the current DNA/RNA synthesizers yielding a large variety of unique 5′-polyphosphorylated oligonucleotides. Using this approach, we accomplished the synthesis of chemically modified 5′-triphosphate oligonucleotides that were annealed to form small-interfering RNAs

  描述了用于5'-三磷酸和5'-二磷酸寡核苷酸的平行和高通量固相合成的全自动化学方法。首先使用标准的自动化DNA / RNA固相合成程序构建所需的全长寡核苷酸。然后，在相同的色谱柱和仪器上，不间断的连续循环的有效实施提供了相应的未修饰或化学修饰的5'-三磷酸酯和5'-二磷酸酯。该方法可轻松转换为可扩展的高通量合成方案，与目前的DNA / RNA合成仪兼容，可产生多种独特的5'-多磷酸化寡核苷酸。使用这种方法，我们完成了化学修饰的5'-三磷酸寡核苷酸的合成，将其退火以形成小干扰RNA（ppp-siRNA），这是一类可能令人感兴趣的新型RNAi治疗工具。5'-三磷酸基团附着到siRNA构建体的过客链上，不会引起体外RNAi介导的基因沉默活性的显着改善，也不会引起强烈的特异性体外RIG-I激活。报道的方法将能够筛选许多经过化学修饰的ppp-siRNA，从而产生新型的双功能RNAi治疗平台。5'-三
• 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.