5-[2-(4-tert-butyl-2-oxopyrrolidin-1-yl)ethoxy]-2-fluorobenzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[2-(4-tert-butyl-2-oxopyrrolidin-1-yl)ethoxy]-2-fluorobenzonitrile
• 英文别名: 5-[2-(4-Tert-butyl-2-oxopyrrolidin-1-yl)ethoxy]-2-fluorobenzonitrile
• 化学式: C₁₇H₂₁FN₂O₂
• 分子量: 304.364
• InChiKey: ZXBQUZQFTWNQON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  53.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氟-5-羟基苯甲腈 在 sodium hydride 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 34.58h， 生成 5-[2-(4-tert-butyl-2-oxopyrrolidin-1-yl)ethoxy]-2-fluorobenzonitrile
  参考文献：
  名称：

  Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA₂)

  摘要：

  Lp-PLA(2) has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA(2). The starting fragment hit was discovered through an X-ray fragment screen and showed no activity in the bioassay (IC50 > 1 mM). The fragment hit was optimized using a variety of structure-based drug design techniques, including virtual screening, fragment merging, and improvement of shape complementarity. A novel series of Lp-PLA(2) inhibitors was generated with low lipophilicity and a promising pharmacokinetic profile.

  DOI：

  10.1021/acs.jmedchem.6b01427

文献信息

• Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA₂)
  作者：Alison J.-A. Woolford、Philip J. Day、Véronique Bénéton、Valerio Berdini、Joseph E. Coyle、Yann Dudit、Pascal Grondin、Pascal Huet、Lydia Y. W. Lee、Eric S. Manas、Rachel L. McMenamin、Christopher W. Murray、Lee W. Page、Vipulkumar K. Patel、Florent Potvain、Sharna J. Rich、Yingxia Sang、Don O. Somers、Lionel Trottet、Zehong Wan、Xiaomin Zhang

  DOI：10.1021/acs.jmedchem.6b01427

  日期：2016.12.8

  Lp-PLA(2) has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA(2). The starting fragment hit was discovered through an X-ray fragment screen and showed no activity in the bioassay (IC50 > 1 mM). The fragment hit was optimized using a variety of structure-based drug design techniques, including virtual screening, fragment merging, and improvement of shape complementarity. A novel series of Lp-PLA(2) inhibitors was generated with low lipophilicity and a promising pharmacokinetic profile.