8-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-1,3,8-triaza-spiro[4.5]decan-4-one | 170921-52-5

• 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]-1,3,8-triaza-spiro[4.5]decan-4-one
• 英文别名: 8-[4-(4-fluorophenyl)-4-oxobutyl]-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 170921-52-5
• 化学式: C₁₇H₂₂FN₃O₂
• 分子量: 319.379
• InChiKey: UFSMXFRTFHFHRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-1,3,8-triaza-spiro[4.5]decan-4-one 、 碘甲烷 在 氢氧化钾 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 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
• 作为产物：
  描述：

  4-氨基-1-苄基哌啶-4-甲腈 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 硫酸 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 25.0~80.0 ℃ 、275.79 kPa 条件下， 反应 70.0h， 生成 8-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-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

• SUBSTITUIERTE 1,3,8-TRIAZA-SPIRO(4,5)-DECAN-4-ON-DERIVATE ALS VORSTUFEN ZUR HERSTELLUNG VON PHARMAZEUTIKA
  申请人：CIS BIO INTERNATIONAL

  公开号：EP0745082A1

  公开（公告）日：1996-12-04
• [DE] SUBSTITUIERTE 1,3,8-TRIAZA-SPIRO(4,5)-DECAN-4-ON-DERIVATE ALS VORSTUFEN ZUR HERSTELLUNG VON PHARMAZEUTIKA<br/>[EN] SUBSTITUTED 1,3,8-TRIAZA-SPIRO(4,5)-DECAN-4-ONE DERIVATIVES USEFUL AS PRELIMINARY STAGES IN THE PRODUCTION OF PHARMACEUTICALS<br/>[FR] DERIVES SUBSTITUES DE 1,3,8-TRIAZA-SPIRO(4,5)-DECAN-4-ONE UTILES COMME PROGENITEURS DE PRODUITS PHARMACEUTIQUES
  申请人：——

  公开号：WO1995022544A2

  公开（公告）日：1995-08-24

  [EN] Compounds having the general formula (I) are useful as preliminary stages in the production of new pharmaceuticals. Said pharmaceuticals are useful as neuroleptic or analgesic agents or as pharmaceuticals in nuclear medicine.
  [FR] Des composés ayant la formule générale (I) sont utiles comme progéniteurs de nouveaux produits pharmaceutiques. Ces produits pharmaceutiques sont utilisés comme agents neuroleptiques ou analgésiques ou comme produits pharmaceutiques en médecine nucléaire.
  [DE] Die Erfindung betrifft Verbindungen der allgemeinen Formel (I) als Vorstufen zur Herstellung neuer Pharmazeutika. Die genannten Pharmazeutika werden verwendet als Neuroleptika, Analgetika oder als Pharmaka in der Nuklearmedizin.
• Spiperone:  Influence of Spiro Ring Substituents on 5-HT_2A Serotonin Receptor Binding
  作者：Kamel A. Metwally、Malgorzata Dukat、Christina T. Egan、Carol Smith、Ann DuPre、Colleen B. Gauthier、Katharine Herrick-Davis、Milt Teitler、Richard A. Glennon

  DOI：10.1021/jm980452a

  日期：1998.12.1

  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.