8-[4-(4-氟苯基)-4-氧代丁基]-3-[2-(4-硝基苯基)乙基]-1-苯基-1,3,8-三氮杂螺[4.5]癸烷-4-酮 | 136247-18-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 8-[4-(4-氟苯基)-4-氧代丁基]-3-[2-(4-硝基苯基)乙基]-1-苯基-1,3,8-三氮杂螺[4.5]癸烷-4-酮
• 英文名称: 8-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-3-[2-(4-nitro-phenyl)-ethyl]-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one
• 英文别名: 8-[4-(4-Fluorophenyl)-4-oxobutyl]-3-[2-(4-nitrophenyl)ethyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 136247-18-2
• 化学式: C₃₁H₃₃FN₄O₄
• mdl: MFCD09952256
• 分子量: 544.626
• InChiKey: VAROERVHUKRDNF-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于丙酮、氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.354
• 拓扑面积：
  89.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-[4-(4-氟苯基)-4-氧代丁基]-3-[2-(4-硝基苯基)乙基]-1-苯基-1,3,8-三氮杂螺[4.5]癸烷-4-酮 在 盐酸 、 铁粉 作用下， 生成 N-(对氨基苯乙基)螺哌隆
  参考文献：
  名称：

  Practical Synthesis ofp‐Aminophenethylspiperone (NAPS), a High‐Affinity, Selective D₂‐Dopamine Receptor Antagonist

  摘要：

  Because attempts to scale up the published synthetic preparation of p-aminophenethylspiperone (NAPS) by N-alkylation of spiperone with 4-nitrophenethyl bromide followed by reduction gave poor yields and difficulties during purification, an alternative synthetic approach has been developed. Use of 4-(N-tert-butyloxycarbonyl) aminophenethyl bromide to alkylate spiperone followed by the Boc group deprotection gave NAPS in 56% yield. This procedure provides an improved and efficient synthesis of the important high-affinity, selective D-2-dopamine receptor antagonist NAPS.

  DOI：

  10.1080/00397910701821135
• 作为产物：
  描述：

  4-硝基苯乙基溴 、 螺哌隆 在 氢氧化钾 、 四丁基硫酸氢铵 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以1.3 g的产率得到8-[4-(4-氟苯基)-4-氧代丁基]-3-[2-(4-硝基苯基)乙基]-1-苯基-1,3,8-三氮杂螺[4.5]癸烷-4-酮
  参考文献：
  名称：

  Fluorescent probes for dopamine receptors: synthesis and characterization of fluorescein and 7-nitrobenz-2-oxa-1,3-diazol-4-yl conjugates of D-1 and D-2 receptor ligands

  摘要：

  Fluorescent probes have been designed and developed for dopamine D-1 and D-2 receptors. Fluorescein and/or NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) derivatives of PPHT (D-2 agonist), spiperone (D-2 antagonist), SKF 38393 (D-1 agonist), and SKF 83566 (D-1 antagonist) were synthesized via their amino-functionalized analogues and all ligands were pharmacologically evaluated by measuring their ability to displace [H-3]SCH 23390 and [H-3]spiperone from D-1 and D-2 receptor sites in caudate putamen of monkeys (Macaca fascicularis). The fluorescein derivatives of PPHT and SKF 83566 and the NBD derivatives of spiperone and SKF 83566 retained the high affinity and selectivity of the parent ligands. The NBD derivatives of PPHT showed higher D-2 receptor affinity and selectivity than their parent ligands. The enantiomers of the fluorescent derivatives of PPHT were also synthesized and were found to exhibit stereoselectivity in binding to the D-2 receptor, with the S enantiomers having a considerably higher affinity than their R analogues. In contrast to these results, the fluorescein derivative of SKF 38393 showed only a low affinity for the D-1 receptor. These fluorescein- and NBD-coupled D-1 and D-2 receptor ligands have considerable significance as potential probes in the study of distribution of the receptors at the cellular/subcellular level and of their mobility in membranes in normal/diseased states by use of fluorescence microscopic and fluorescence photobleaching recovery techniques, respectively. The development of these novel fluorescent probes should also provide new leads for the design and synthesis of additional fluorescent ligands with better fluorescent properties and/or higher affinity/selectivity for the DA receptors.

  DOI：

  10.1021/jm00115a012

文献信息

• Fluorescent probes for dopamine receptors: synthesis and characterization of fluorescein and 7-nitrobenz-2-oxa-1,3-diazol-4-yl conjugates of D-1 and D-2 receptor ligands
  作者：Venkatesalu Bakthavachalam、Nandkishore Baindur、Bertha K. Madras、John L. Neumeyer

  DOI：10.1021/jm00115a012

  日期：1991.11

  Fluorescent probes have been designed and developed for dopamine D-1 and D-2 receptors. Fluorescein and/or NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) derivatives of PPHT (D-2 agonist), spiperone (D-2 antagonist), SKF 38393 (D-1 agonist), and SKF 83566 (D-1 antagonist) were synthesized via their amino-functionalized analogues and all ligands were pharmacologically evaluated by measuring their ability to displace [H-3]SCH 23390 and [H-3]spiperone from D-1 and D-2 receptor sites in caudate putamen of monkeys (Macaca fascicularis). The fluorescein derivatives of PPHT and SKF 83566 and the NBD derivatives of spiperone and SKF 83566 retained the high affinity and selectivity of the parent ligands. The NBD derivatives of PPHT showed higher D-2 receptor affinity and selectivity than their parent ligands. The enantiomers of the fluorescent derivatives of PPHT were also synthesized and were found to exhibit stereoselectivity in binding to the D-2 receptor, with the S enantiomers having a considerably higher affinity than their R analogues. In contrast to these results, the fluorescein derivative of SKF 38393 showed only a low affinity for the D-1 receptor. These fluorescein- and NBD-coupled D-1 and D-2 receptor ligands have considerable significance as potential probes in the study of distribution of the receptors at the cellular/subcellular level and of their mobility in membranes in normal/diseased states by use of fluorescence microscopic and fluorescence photobleaching recovery techniques, respectively. The development of these novel fluorescent probes should also provide new leads for the design and synthesis of additional fluorescent ligands with better fluorescent properties and/or higher affinity/selectivity for the DA receptors.
• Practical Synthesis of<i>p</i>‐Aminophenethylspiperone (NAPS), a High‐Affinity, Selective D₂‐Dopamine Receptor Antagonist
  作者：Chunyang Jin、Louise D. Mayer、Anita H. Lewin、Kenneth S. Rehder、George A. Brine

  DOI：10.1080/00397910701821135

  日期：2008.2.13

  Because attempts to scale up the published synthetic preparation of p-aminophenethylspiperone (NAPS) by N-alkylation of spiperone with 4-nitrophenethyl bromide followed by reduction gave poor yields and difficulties during purification, an alternative synthetic approach has been developed. Use of 4-(N-tert-butyloxycarbonyl) aminophenethyl bromide to alkylate spiperone followed by the Boc group deprotection gave NAPS in 56% yield. This procedure provides an improved and efficient synthesis of the important high-affinity, selective D-2-dopamine receptor antagonist NAPS.