8-[4-(4-fluoro-phenyl)-4-oxo-butyl]-1-methyl-1,3,8-triaza-spiro[4.5]decan-4-one | 217635-62-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-[4-(4-fluoro-phenyl)-4-oxo-butyl]-1-methyl-1,3,8-triaza-spiro[4.5]decan-4-one
• 英文别名: V68MR69Ldz；8-[4-(4-fluorophenyl)-4-oxobutyl]-1-methyl-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 217635-62-6
• 化学式: C₁₈H₂₄FN₃O₂
• 分子量: 333.406
• InChiKey: GRADLHIYNHRBCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-苄基哌啶酮 在 palladium on activated charcoal 盐酸 、 氢氧化钾 、 sodium tetrahydroborate 、 硫酸 、 氢气 、 potassium carbonate 、 氯化铵 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 25.0~80.0 ℃ 、275.79 kPa 条件下， 反应 118.5h， 生成 8-[4-(4-fluoro-phenyl)-4-oxo-butyl]-1-methyl-1,3,8-triaza-spiro[4.5]decan-4-one
  参考文献：
  名称：

  Spiperone:  Influence of Spiro Ring Substituents on 5-HT_2A Serotonin Receptor Binding

  摘要：

  Spiperone (1) is a widely used pharmacological tool that acts as a potent dopamine D-2, serotonin 5-HT1A, and serotonin 5-HT2A antagonist. Although spiperone also binds at 5-HT2C receptors, it is one of the very few agents that display some (ca. 1000-fold) binding selectivity for 5-HT2A versus 5-HT2C receptors and, hence, might serve as a useful template for the development of novel 5-HT2A antagonists if the impact of its various substituent groups on binding was known. In the present investigation we focused on the 1,3,8-triazaspiro[4.5]decanone portion of spiperone and found that replacement of the N-1-phenyl group with a methyl group only slightly decreased affinity for cloned rat 5-HT2A receptors. However, N-1-methyl derivatives displayed significantly reduced affinity for 5-HT1A, 5-HT2C, and dopamine D-2 receptors. Several representative examples were shown to behave as 5-HT2 antagonists. As such, N-1-alkyl analogues of spiperone may afford entry into a novel series of 5-HT2A-selective antagonists.

  DOI：

  10.1021/jm980452a

文献信息

• AGENT FOR PROPHYLAXIS AND TREATMENT OF PANCREATITIS
  申请人：Yamaguchi Isamu

  公开号：US20090075974A1

  公开（公告）日：2009-03-19

  Disclosed is a pharmaceutical composition for prophylaxis and treatment of pancreatitis comprising a 5-HT2A receptor antagonist as an effective component, wherein the binding activity (pKi) of the 5-HT2A receptor antagonist to a 5-HT2A receptor is higher at least by 1.0 than the binding activities to a 5-HT2B receptor and a 5-HT2C receptor. Preferably the binding activity (pKi) of the 5-HT2A receptor antagonist to the 5-HT2A receptor is at least 7.0, and more preferably at least 8.0. The present invention also provides a method of identifying a candidate substance for prophylactic and therapeutic agent for pancreatitis, comprising determining whether a test substance has a 5-HT2A receptor antagonistic activity.