4-[6-Fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-ylmethyl]-morpholine | 1020092-87-8

• 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: 4-[6-Fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-ylmethyl]-morpholine
• 英文别名: 4-[[6-fluoro-2,2-bis(4-fluorophenyl)-1,3-benzodioxol-5-yl]methyl]morpholine
• CAS: 1020092-87-8
• 化学式: C₂₄H₂₀F₃NO₃
• 分子量: 427.423
• InChiKey: NBHSLCWSMRDUQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  [6-fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholin-4-yl-methanone 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以8%的产率得到4-[6-Fluoro-2,2-bis-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-ylmethyl]-morpholine
  参考文献：
  名称：

  Benzodioxoles: Novel Cannabinoid-1 Receptor Inverse Agonists for the Treatment of Obesity

  摘要：

  The application of the evolutionary fragment-based de novo design tool TOPology Assigning System (TOPAS), starting from a known CBIR (CB-1 receptor) ligand, followed by further refinement principles, including pharmacophore compliance, chemical tractability, and drug likeness, allowed the identification of benzodioxoles as a novel CB I R inverse agonist series. Extensive multidimensional optimization was rewarded by the identification of promising lead compounds, showing in vivo activity. These compounds reversed the CP-55940-induced hypothermia in Naval Medical Research Institute (NMRI) mice and reduced body-weight gain, as well as fat mass, in diet-induced obese Sprague-Dawley rats. Herein, we disclose the tools and strategies that were employed for rapid hit identification, synthesis and generation of structure-activity relationships, ultimately leading to the identification of (+)-[(R)-2-(2,4-dichloride-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholin-4-yl-metha- none (R)-14g. Biochemical, pharmacokinetic, and pharmacodynamic characteristics of (R)-14g are discussed.

  DOI：

  10.1021/jm701487t

文献信息

• Benzodioxoles: Novel Cannabinoid-1 Receptor Inverse Agonists for the Treatment of Obesity
  作者：Leo Alig、Jochem Alsenz、Mirjana Andjelkovic、Stefanie Bendels、Agnès Bénardeau、Konrad Bleicher、Anne Bourson、Pascale David-Pierson、Wolfgang Guba、Stefan Hildbrand、Dagmar Kube、Thomas Lübbers、Alexander V. Mayweg、Robert Narquizian、Werner Neidhart、Matthias Nettekoven、Jean-Marc Plancher、Cynthia Rocha、Mark Rogers-Evans、Stephan Röver、Gisbert Schneider、Sven Taylor、Pius Waldmeier

  DOI：10.1021/jm701487t

  日期：2008.4.1

  The application of the evolutionary fragment-based de novo design tool TOPology Assigning System (TOPAS), starting from a known CBIR (CB-1 receptor) ligand, followed by further refinement principles, including pharmacophore compliance, chemical tractability, and drug likeness, allowed the identification of benzodioxoles as a novel CB I R inverse agonist series. Extensive multidimensional optimization was rewarded by the identification of promising lead compounds, showing in vivo activity. These compounds reversed the CP-55940-induced hypothermia in Naval Medical Research Institute (NMRI) mice and reduced body-weight gain, as well as fat mass, in diet-induced obese Sprague-Dawley rats. Herein, we disclose the tools and strategies that were employed for rapid hit identification, synthesis and generation of structure-activity relationships, ultimately leading to the identification of (+)-[(R)-2-(2,4-dichloride-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholin-4-yl-metha- none (R)-14g. Biochemical, pharmacokinetic, and pharmacodynamic characteristics of (R)-14g are discussed.