3-{4-[4-(3-trifluoromethylphenyl)piperazin-1-yl]butyl}-8-phenyl-1,3-diazaspiro[4,5]decan-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-{4-[4-(3-trifluoromethylphenyl)piperazin-1-yl]butyl}-8-phenyl-1,3-diazaspiro[4,5]decan-2,4-dione
• 英文别名: 8-Phenyl-3-[4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]butyl]-1,3-diazaspiro[4.5]decane-2,4-dione；8-phenyl-3-[4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]butyl]-1,3-diazaspiro[4.5]decane-2,4-dione
• 化学式: C₂₉H₃₅F₃N₄O₂
• 分子量: 528.618
• InChiKey: KUFHUQCIJOTNEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  55.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-{4-[4-(3-trifluoromethylphenyl)piperazin-1-yl]butyl}-8-phenyl-1,3-diazaspiro[4,5]decan-2,4-dione 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 3-{4-[4-(3-trifluoromethylphenyl)piperazin-1-yl]butyl}-8-phenyl-1,3-diazaspiro[4,5]decan-2,4-dione hydrochloride
  参考文献：
  名称：

  Novel spirohydantoin derivative as a potent multireceptor-active antipsychotic and antidepressant agent

  摘要：

  A series of novel spirohydantoin derivatives with arylpiperazinylbutyl moiety were synthesized and evaluated for serotonin 5-HT1A, 5-HT2A, 5-HT7 and dopamine D-2 receptors. Based on these data, four compounds were selected for further binding affinity assays on dopamine D-1, D-3, D-4, and 5-HT2C, 5-HT6 as well as adrenergic alpha 1 and alpha(2C) receptors, which are involved in various CNS diseases such as schizophrenia, anxiety and/or depression. The compound 14, 1-{4-[4-(2-metoxyphe-nyl) piperazin-1-yl] butyl}-3',4'-dihydro-2H, 2'H, 5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, with the most promising functional profile, mixed 5-HT2A/D-2 antagonist and 5-HT1A partial agonist, was selected. In the mouse D-amphetamine-induced locomotor hyperactivity model, compound 14 produced antipsychotic-like activity, which is devoid of cataleptogenic effects and in the forced swim test in mice, it showed a significant antidepressant-like effect unlike the reference drug aripiprazole. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.026
• 作为产物：
  描述：

  8-苯基-1,3-二氮杂螺[4.5]癸烷-2,4-二酮 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 生成 3-{4-[4-(3-trifluoromethylphenyl)piperazin-1-yl]butyl}-8-phenyl-1,3-diazaspiro[4,5]decan-2,4-dione
  参考文献：
  名称：

  Novel spirohydantoin derivative as a potent multireceptor-active antipsychotic and antidepressant agent

  摘要：

  A series of novel spirohydantoin derivatives with arylpiperazinylbutyl moiety were synthesized and evaluated for serotonin 5-HT1A, 5-HT2A, 5-HT7 and dopamine D-2 receptors. Based on these data, four compounds were selected for further binding affinity assays on dopamine D-1, D-3, D-4, and 5-HT2C, 5-HT6 as well as adrenergic alpha 1 and alpha(2C) receptors, which are involved in various CNS diseases such as schizophrenia, anxiety and/or depression. The compound 14, 1-{4-[4-(2-metoxyphe-nyl) piperazin-1-yl] butyl}-3',4'-dihydro-2H, 2'H, 5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, with the most promising functional profile, mixed 5-HT2A/D-2 antagonist and 5-HT1A partial agonist, was selected. In the mouse D-amphetamine-induced locomotor hyperactivity model, compound 14 produced antipsychotic-like activity, which is devoid of cataleptogenic effects and in the forced swim test in mice, it showed a significant antidepressant-like effect unlike the reference drug aripiprazole. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.026

文献信息

• An insight into the structure of 5-spiro aromatic derivatives of imidazolidine-2,4-dione, a new group of very potent inhibitors of tumor multidrug resistance in T-lymphoma cells
  作者：Ewa Żesławska、Katarzyna Kucwaj-Brysz、Annamária Kincses、Gabriella Spengler、Ewa Szymańska、Anna Czopek、Małgorzata Anna Marć、Aneta Kaczor、Wojciech Nitek、Enrique Domínguez-Álvarez、Gniewomir Latacz、Katarzyna Kieć-Kononowicz、Jadwiga Handzlik

  DOI：10.1016/j.bioorg.2021.104735

  日期：2021.4

  have been performed. The ability to inhibit the tumor multidrug resistance (MDR) efflux pump P-glycoprotein (P-gp, ABCB1) overexpressed in mouse T-lymphoma cells was investigated. The cytotoxic and antiproliferative actions of the compounds on both the reference and the ABCB1-overproducing cells were also examined. The pharmacophore-based molecular modeling studies have been performed. ADMET properties

  已经探索了 5-spiroimidazolidine-2,4-diones ( 6 – 22 )的一系列 17 芳基哌嗪衍生物，包括 (i) 第 5 位芳环的数量，(ii) 接头长度的变化，以及 (iii) 连接的芳基哌嗪末端片段的种类和位置。代表性化合物（8、10、14和18）的合成 ( 6 – 16 ) 和 X 射线晶体学研究) 已执行。研究了抑制在小鼠 T 淋巴瘤细胞中过表达的肿瘤多药耐药 (MDR) 外排泵 P-糖蛋白 (P-gp, ABCB1) 的能力。还检查了化合物对参考细胞和 ABCB1 过度产生细胞的细胞毒性和抗增殖作用。已经进行了基于药效团的分子建模研究。ADMET性质体外选择的最活跃的衍生物（的6，11和12）已被确定。所有化合物，不包括18，以比参考维拉帕米更高的效力抑制癌症 P-gp 外排泵。与胺的烷基取代基的螺芴衍生物在位置1处，和在位置3（甲基6 - 16），发生在MDR
• Novel spirohydantoin derivative as a potent multireceptor-active antipsychotic and antidepressant agent
  作者：Anna Czopek、Marcin Kołaczkowski、Adam Bucki、Hanna Byrtus、Maciej Pawłowski、Grzegorz Kazek、Andrzej J. Bojarski、Agata Piaskowska、Justyna Kalinowska-Tłuścik、Anna Partyka、Anna Wesołowska

  DOI：10.1016/j.bmc.2015.04.026

  日期：2015.7

  A series of novel spirohydantoin derivatives with arylpiperazinylbutyl moiety were synthesized and evaluated for serotonin 5-HT1A, 5-HT2A, 5-HT7 and dopamine D-2 receptors. Based on these data, four compounds were selected for further binding affinity assays on dopamine D-1, D-3, D-4, and 5-HT2C, 5-HT6 as well as adrenergic alpha 1 and alpha(2C) receptors, which are involved in various CNS diseases such as schizophrenia, anxiety and/or depression. The compound 14, 1-4-[4-(2-metoxyphe-nyl) piperazin-1-yl] butyl}-3',4'-dihydro-2H, 2'H, 5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, with the most promising functional profile, mixed 5-HT2A/D-2 antagonist and 5-HT1A partial agonist, was selected. In the mouse D-amphetamine-induced locomotor hyperactivity model, compound 14 produced antipsychotic-like activity, which is devoid of cataleptogenic effects and in the forced swim test in mice, it showed a significant antidepressant-like effect unlike the reference drug aripiprazole. (C) 2015 Elsevier Ltd. All rights reserved.