cyclohexylmethyl (2R,3R,4R,5R,6R)-5-acetamido-4-amino-2,3-difluoro-6-((1R,2R)-1,2,3-trihydroxypropyl)tetrahydro-2H-pyran-2-carboxylate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: cyclohexylmethyl (2R,3R,4R,5R,6R)-5-acetamido-4-amino-2,3-difluoro-6-((1R,2R)-1,2,3-trihydroxypropyl)tetrahydro-2H-pyran-2-carboxylate
• 英文别名: cyclohexylmethyl (2R,3R,4R,5R,6R)-5-acetamido-4-amino-2,3-difluoro-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate
• 化学式: C₁₈H₃₀F₂N₂O₇
• 分子量: 424.442
• InChiKey: VUYBRLJFGODGTI-QZNQKGLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  151
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 cyclohexylmethyl (2R,3R,4R,5R,6R)-5-acetamido-4-amino-2,3-difluoro-6-((1R,2R)-1,2,3-trihydroxypropyl)tetrahydro-2H-pyran-2-carboxylate
  参考文献：
  名称：

  Assessing the oral bioavailability of difluorosialic acid prodrugs, potent viral neuraminidase inhibitors, using a snapshot PK screening assay

  摘要：

  Difluorosialic acids (DFSAs) are potent inhibitors of viral neuraminidase that demonstrate activity against oseltamivir- and zanamivir-resistant strains of influenza. Unfortunately, low oral bioavailability precludes their development as second generation neuraminidase inhibitors for treating influenza as this leaves them unsuitable for use in an oral formulation. Herein is described the preparation of a series of DFSA prodrugs designed to increase oral bioavailability. These prodrugs were evaluated using a snapshot PK screen and stability tests, with successful candidates being further assessed with a full pharmacokinetic workup. These new prodrugs increased oral bioavailability by up to three times that seen for the parent DFSAs. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.059