(3aS,4R,7aS)-6-(2,5-Dimethoxy-benzyloxymethyl)-2,2-diethyl-7-fluoro-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-ol | 1053732-65-2

• 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: (3aS,4R,7aS)-6-(2,5-Dimethoxy-benzyloxymethyl)-2,2-diethyl-7-fluoro-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-ol
• 英文别名: (3aS,4R,7aS)-6-[(2,5-dimethoxyphenyl)methoxymethyl]-2,2-diethyl-7-fluoro-3a,4,5,7a-tetrahydro-1,3-benzodioxol-4-ol
• CAS: 1053732-65-2
• 化学式: C₂₁H₂₉FO₆
• 分子量: 396.456
• InChiKey: LFYCNYDYICDSJB-LSTHTHJFSA-N

物化性质

• 沸点：
  508.5±50.0 °C(predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3aS,4R,7aS)-6-(2,5-Dimethoxy-benzyloxymethyl)-2,2-diethyl-7-fluoro-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-ol 在 dimethyl sulfide borane 、 potassium hydrogencarbonate 、 三乙胺 、 三氟甲烷磺酸甲酯 作用下， 以 二氯甲烷 为溶剂， 反应 2.84h， 生成 [(1S,5S,6S)-5-(1-Ethyl-propoxy)-4-fluoro-7-oxa-bicyclo[4.1.0]hept-3-en-3-yl]-methanol
  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
• 作为产物：
  描述：

  (3aS,4R,7aS)-6-(2,5-Dimethoxy-benzyloxymethyl)-7-fluoro-4-methoxymethoxy-2,2-dimethyl-3a,4,5,7a-tetrahydro-benzo[1,3]dioxole 在 甲醇 、 4 A molecular sieve 、 对甲苯磺酸 作用下， 反应 12.0h， 生成 (3aS,4R,7aS)-6-(2,5-Dimethoxy-benzyloxymethyl)-2,2-diethyl-7-fluoro-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-ol
  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