(6-fluoro-2,2-diphenyl-benzo[1,3]dioxole-5-yl)-piperidin-1-yl-methanone | 656804-47-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (6-fluoro-2,2-diphenyl-benzo[1,3]dioxole-5-yl)-piperidin-1-yl-methanone
• 英文别名: (6-fluoro-2,2-diphenyl-benzo[1,3]dioxol-5-yl)-piperidin-1-yl-methanone；(6-Fluoro-2,2-diphenylbenzo[d][1,3]dioxol-5-yl)(piperidin-1-yl)methanone；(6-fluoro-2,2-diphenyl-1,3-benzodioxol-5-yl)-piperidin-1-ylmethanone
• CAS: 656804-47-6
• 化学式: C₂₅H₂₂FNO₃
• 分子量: 403.453
• InChiKey: XTESHPWNXCEONX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6-fluoro-2,2-diphenyl-benzo[1,3]dioxole-5-yl)-piperidin-1-yl-methanone 在 三乙基硅烷 、 三氟乙酸 作用下， 反应 4.0h， 以69%的产率得到(2-fluoro-4,5-dihydroxyphenyl)piperidin-1-ylmethanone
  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
• 作为产物：
  描述：

  哌啶 、 6-fluoro-2,2-diphenylbenzo[1,3]dioxole-5-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (6-fluoro-2,2-diphenyl-benzo[1,3]dioxole-5-yl)-piperidin-1-yl-methanone
  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

• [EN] NOVEL BENZODIOXOLES<br/>[FR] NOUVEAUX BENZODIOXOLES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004013120A1

  公开（公告）日：2004-02-12

  The present invention relates to compound of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, and X are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases, which are associated with the modulation of CB1 receptors.

  本发明涉及具有式（I）的化合物，其中R1、R2、R3、R4、R5、R6、R7和X如描述和权利要求中所定义，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与CB1受体调节相关的疾病。
• Spiro-pentacyclic compounds
  申请人：Plancher Jean-Marc

  公开号：US20050165012A1

  公开（公告）日：2005-07-28

  The present invention relates to compounds of the formula (I) and pharmaceutically acceptable salts thereof, for use as therapeutically active substances. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors including obesity.

  本发明涉及公式（I）的化合物及其药学上可接受的盐，用作治疗活性物质。这些化合物可用于治疗和/或预防与CB1受体调节相关的疾病，包括肥胖症。
• Benzodioxole derivatives
  申请人：Alanine Alexander

  公开号：US20050143373A1

  公开（公告）日：2005-06-30

  The present invention relates to compounds of the general formula and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases such as obesity by selective modulation of CB1 receptors.

  本发明涉及一般式的化合物及其药学上可接受的盐。该化合物通过选择性调节CB1受体，对于治疗和/或预防肥胖等疾病是有用的。
• NOVEL BENZODIOXOLES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1532132B1

  公开（公告）日：2008-03-19
• SPIRO-BENZODIOXOLES AND THEIR USE AS CB1 ANTAGONISTS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1716132A2

  公开（公告）日：2006-11-02