(3R,4R,5S)-4-acetamido-3-(pentan-3-yloxy)-5-((3-phenylpropyl)amino)cyclohex-1-enecarboxylic acid

• 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: (3R,4R,5S)-4-acetamido-3-(pentan-3-yloxy)-5-((3-phenylpropyl)amino)cyclohex-1-enecarboxylic acid
• 英文别名: (3R,4R,5S)-4-acetamido-3-pentan-3-yloxy-5-(3-phenylpropylamino)cyclohexene-1-carboxylic acid
• 化学式: C₂₃H₃₄N₂O₄
• 分子量: 402.534
• InChiKey: XSHYAKVACIHYRB-BHDDXSALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  29.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  87.66
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  磷酸奥司他韦 在 sodium cyanoborohydride 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 10.0h， 生成 (3R,4R,5S)-4-acetamido-3-(pentan-3-yloxy)-5-((3-phenylpropyl)amino)cyclohex-1-enecarboxylic acid
  参考文献：
  名称：

  Discovery of N-Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase

  摘要：

  To discover group-1-specific neuraminidase (NA) inhibitors that are especially involved in combating the H5N1 virus, two series of oseltamivir derivatives were designed and synthesized by targeting the 150-cavity. Among these, compound 20l was the most potent N1-selective inhibitor, with IC50 values of 0.0019, 0.0038, and 0.0067 mu M against NAs from three H5N1 viruses. These values are better than those of oseltamivir carboxylate. Compound 32 was another potent N1-selective inhibitor that exhibited a 12-fold increase in activity against the H274Y mutant relative to oseltamivir carboxylate. Molecular docking studies revealed that the 150-cavity was an auxiliary binding site that may contribute to the high selectivity of these compounds. The present work is a significant breakthrough in the discovery of potent group-1-specific neuraminidase inhibitors, which may be further investigated for the treatment of infection by the H5N1 virus.

  DOI：

  10.1021/jm500892k

文献信息

• Discovery of N-Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase
  作者：Yuanchao Xie、Dongqing Xu、Bing Huang、Xiuli Ma、Wenbao Qi、Fangyuan Shi、Xinyong Liu、Yingjie Zhang、Wenfang Xu

  DOI：10.1021/jm500892k

  日期：2014.10.23

  To discover group-1-specific neuraminidase (NA) inhibitors that are especially involved in combating the H5N1 virus, two series of oseltamivir derivatives were designed and synthesized by targeting the 150-cavity. Among these, compound 20l was the most potent N1-selective inhibitor, with IC50 values of 0.0019, 0.0038, and 0.0067 mu M against NAs from three H5N1 viruses. These values are better than those of oseltamivir carboxylate. Compound 32 was another potent N1-selective inhibitor that exhibited a 12-fold increase in activity against the H274Y mutant relative to oseltamivir carboxylate. Molecular docking studies revealed that the 150-cavity was an auxiliary binding site that may contribute to the high selectivity of these compounds. The present work is a significant breakthrough in the discovery of potent group-1-specific neuraminidase inhibitors, which may be further investigated for the treatment of infection by the H5N1 virus.