(3R,4R,5S)-4-Acetamido-5-amino-3-(bis(3-phenylpropyl)methoxy)-1-cyclohexene-1-carboxylic Acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (3R,4R,5S)-4-Acetamido-5-amino-3-(bis(3-phenylpropyl)methoxy)-1-cyclohexene-1-carboxylic Acid
• 英文别名: (3R,4R,5S)-4-acetamido-5-amino-3-(1,7-diphenylheptan-4-yloxy)cyclohexene-1-carboxylic acid
• 化学式: C₂₈H₃₆N₂O₄
• 分子量: 464.605
• InChiKey: TXVFAGMTJMJDMF-OYUWMTPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-phenylpropyl-magnesium bromide 在 吡啶 、 4-二甲氨基吡啶 、 氢氧化钾 、 三氟化硼乙醚 、 水 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 32.67h， 生成 (3R,4R,5S)-4-Acetamido-5-amino-3-(bis(3-phenylpropyl)methoxy)-1-cyclohexene-1-carboxylic Acid
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Carbocyclic Influenza Neuraminidase Inhibitors

  摘要：

  A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized anti evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.

  DOI：

  10.1021/jm980162u

文献信息

• Structure−Activity Relationship Studies of Novel Carbocyclic Influenza Neuraminidase Inhibitors
  作者：Choung U. Kim、Willard Lew、Matthew A. Williams、Huiwei Wu、Lijun Zhang、Xiaowu Chen、Paul A. Escarpe、Dirk B. Mendel、W. Graeme Laver、Raymond C. Stevens

  DOI：10.1021/jm980162u

  日期：1998.7.1

  A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized anti evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.