(3R)-3-hydroxy-4-methoxybutanenitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3R)-3-hydroxy-4-methoxybutanenitrile
• 化学式: C₅H₉NO₂
• 分子量: 115.132
• InChiKey: VINMGQFONSAFIQ-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R)-3-hydroxy-4-methoxybutanenitrile 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 0.5h， 生成 (R)-4-amino-1-methoxybutan-2-ol
  参考文献：
  名称：

  Carbamoyl Pyridone HIV-1 Integrase Inhibitors 3. A Diastereomeric Approach to Chiral Nonracemic Tricyclic Ring Systems and the Discovery of Dolutegravir (S/GSK1349572) and (S/GSK1265744)

  摘要：

  We report herein the discovery of the human immunodeficiency virus type-1 (HIV-1) integrase inhibitors dolutegravir (S/GSK1349572) (3) and S/GSK1265744 (4). These drugs stem from a series of carbamoyl pyridone analogues designed using a two-metal chelation model of the integrase catalytic active site. Structure-activity studies evolved a tricyclic series of carbamoyl pyridines that demonstrated properties indicative of once-daily dosing and superior potency against resistant viral strains. An inherent hemiaminal ring fusion stereocenter within the tricyclic carbamoyl pyridone scaffold led to a critical substrate controlled diastereo-selective synthetic strategy whereby chiral information from small readily available amino alcohols was employed to control relative and absolute stereochemistry of the final drug candidates. Modest to extremely high levels of stereochemical control were observed depending on ring size and position of the stereocenter. This approach resulted in the discovery of 3 and 4, which are currently in clinical development.

  DOI：

  10.1021/jm400645w