3-(cyclopentyloxy)-4-(difluoromethoxy)benzaldehyde O-[2-hydroxy-3-(4-hydroxypiperidin-1-yl)propyl]oxime

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(cyclopentyloxy)-4-(difluoromethoxy)benzaldehyde O-[2-hydroxy-3-(4-hydroxypiperidin-1-yl)propyl]oxime
• 化学式: C₂₁H₃₀F₂N₂O₅
• 分子量: 428.476
• InChiKey: HTIQENVVWCWDSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.78
• 重原子数：
  30.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  83.75
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  4-二氟甲氧基-3-羟基苯甲醛 在 盐酸羟胺 、 sodium 、 碳酸氢钠 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.25h， 生成 3-(cyclopentyloxy)-4-(difluoromethoxy)benzaldehyde O-[2-hydroxy-3-(4-hydroxypiperidin-1-yl)propyl]oxime
  参考文献：
  名称：

  Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors

  摘要：

  A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B2 and PDE4C2). Compound 3b, chosen among the synthesized compounds as the most promising in terms of inhibitory activity, selectivity and safety, showed an improved pharmacokinetic profile compared to its non fluorinated analogue. Spontaneous locomotor activity, assessed in an open field apparatus, showed that, differently from rolipram and diazepam, selective PDE4D inhibitors, such as compounds 3b, 5b and 7b, did not affect locomotion, whereas compound 1b showed a tendency to reduce the distance traveled and to prolong the immobility period, possibly due to a poor selectivity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.027

文献信息

• Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors
  作者：Chiara Brullo、Matteo Massa、Carla Villa、Roberta Ricciarelli、Daniela Rivera、Maria Adelaide Pronzato、Ernesto Fedele、Elisabetta Barocelli、Simona Bertoni、Lisa Flammini、Olga Bruno

  DOI：10.1016/j.bmc.2015.04.027

  日期：2015.7

  A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B2 and PDE4C2). Compound 3b, chosen among the synthesized compounds as the most promising in terms of inhibitory activity, selectivity and safety, showed an improved pharmacokinetic profile compared to its non fluorinated analogue. Spontaneous locomotor activity, assessed in an open field apparatus, showed that, differently from rolipram and diazepam, selective PDE4D inhibitors, such as compounds 3b, 5b and 7b, did not affect locomotion, whereas compound 1b showed a tendency to reduce the distance traveled and to prolong the immobility period, possibly due to a poor selectivity. (C) 2015 Elsevier Ltd. All rights reserved.