N3-(2-propyl)-8-benzyl-1-methyl-1,3,8-triazaspiro<4.5>decan-4-one | 1025980-76-0

• 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: N3-(2-propyl)-8-benzyl-1-methyl-1,3,8-triazaspiro<4.5>decan-4-one
• 英文别名: 8-Benzyl-1-methyl-3-propan-2-yl-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 1025980-76-0
• 化学式: C₁₈H₂₇N₃O
• 分子量: 301.432
• InChiKey: OOYWNRABQZHIEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  26.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N3-(2-propyl)-8-benzyl-1-methyl-1,3,8-triazaspiro<4.5>decan-4-one 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 反应 10.0h， 以76%的产率得到3-异丙基-1-甲基-1,3,8-三氮杂-螺[4.5]癸烷-4-酮
  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
• 作为产物：
  描述：

  8-benzyl-1-methyl-1,3,8-triazaspiro<4.5>dec-2-en-4-one 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 13.08h， 生成 N3-(2-propyl)-8-benzyl-1-methyl-1,3,8-triazaspiro<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