8-苯乙基-1-苯基-1,3,8-三氮杂-螺[4.5]癸烷-4-酮 | 1048-17-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 8-苯乙基-1-苯基-1,3,8-三氮杂-螺[4.5]癸烷-4-酮
• 英文名称: 8-phenethyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one
• 英文别名: 8-Phenethyl-4-phenyl-1-oxo-2,4,8-triazaspiro<4.5>decan；1-phenyl-8-(2-phenylethyl)-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 1048-17-5
• 化学式: C₂₁H₂₅N₃O
• 分子量: 335.449
• InChiKey: VBFCKBBGHPJVIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对甲磺酸苯乙酯 、 1-苯基-1,3,8-三唑螺环(4,5)十烷-4-酮 反应 2.0h， 以44%的产率得到8-苯乙基-1-苯基-1,3,8-三氮杂-螺[4.5]癸烷-4-酮
  参考文献：
  名称：

  Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist

  摘要：

  DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5-HT1C/2 serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT1C- or 5-HT2-mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT1C- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT1A serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT1C sites and (b) it has been used as a ''5-HT2-selective'' antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure-affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4-fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one(26), was shown to bind at 5-HT2 sites with high affinity (K(i) = 2 nM) and >2,000-fold selectivity versus 5-HT1C sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT1C-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.

  DOI：

  10.1021/jm00069a010

文献信息

• Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors
  作者：Emmanuel Pinard、Simona M. Ceccarelli、Henri Stalder、Daniela Alberati

  DOI：10.1016/j.bmcl.2005.09.075

  日期：2006.1

  Screening of the Roche compound library led to the identification of cis-N-(2-phenyt-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform. (c) 2005 Elsevier Ltd. All rights reserved.
• Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist
  作者：Abd M. Ismaiel、Joseph De Los Angeles、Milt Teitler、Stacy Ingher、Richard A. Glennon

  DOI：10.1021/jm00069a010

  日期：1993.8

  DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5-HT1C/2 serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT1C- or 5-HT2-mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT1C- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT1A serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT1C sites and (b) it has been used as a ''5-HT2-selective'' antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure-affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4-fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one(26), was shown to bind at 5-HT2 sites with high affinity (K(i) = 2 nM) and >2,000-fold selectivity versus 5-HT1C sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT1C-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.