2-[4-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-[3-(1-hydroxyethyl)-1-oxidopyridin-1-ium-4-yl]ethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol | 524775-39-1

• 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: 2-[4-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-[3-(1-hydroxyethyl)-1-oxidopyridin-1-ium-4-yl]ethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol
• CAS: 524775-39-1
• 化学式: C₂₆H₂₁F₁₀NO₅
• 分子量: 617.44
• InChiKey: YYRKCTWXRHKWET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  84.4
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  2-[4-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-[3-(1-hydroxyethyl)-1-oxidopyridin-1-ium-4-yl]ethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol 在 吡啶 、 chromium(VI) oxide 、 Celite 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以40%的产率得到1-[4-[2-[3,4-Bis(difluoromethoxy)phenyl]-2-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]ethyl]-1-oxidopyridin-1-ium-3-yl]ethanone
  参考文献：
  名称：

  Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters

  摘要：

  A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported. The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species. The efficacy of L-826,141 is also demonstrated in different in vivo models. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00615-7
• 作为产物：
  描述：

  4-甲基吡啶-5-甲醛 在 2,6-二甲基吡啶 、 甲醇 、 六甲基磷酰三胺 、 manganese(IV) oxide 、 lithium hydroxide 、 sodium tetrahydroborate 、 四丁基氟化铵 、 双(三甲基硅烷基)氨基钾 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 67.08h， 生成 2-[4-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-[3-(1-hydroxyethyl)-1-oxidopyridin-1-ium-4-yl]ethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol
  参考文献：
  名称：

  Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters

  摘要：

  A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported. The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species. The efficacy of L-826,141 is also demonstrated in different in vivo models. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00615-7

文献信息

• Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters
  作者：Richard Frenette、Marc Blouin、Christine Brideau、Nathalie Chauret、Yves Ducharme、Richard W. Friesen、Pierre Hamel、Tom R. Jones、France Laliberté、Chun Li、Paul Masson、Malia McAuliffe、Yves Girard

  DOI：10.1016/s0960-894x(02)00615-7

  日期：2002.10

  A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported. The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species. The efficacy of L-826,141 is also demonstrated in different in vivo models. (C) 2002 Elsevier Science Ltd. All rights reserved.