4-(1,4-dioxa-8-azaspiro<4.5>dec-8-yl)-4'-fluorobutyrophenone | 51787-84-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(1,4-dioxa-8-azaspiro<4.5>dec-8-yl)-4'-fluorobutyrophenone
• 英文别名: 1-(4-fluorophenyl)-4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)butan-1-one；4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-1-(4-fluorophenyl)butan-1-one；4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-1-(4-fluoro-phenyl)-butan-1-one；8-<3-(4-fluorobenzoyl)propyl>-1,4-dioxa-8-azaspiro-<4,5>-decan；4-(1,4-Dioxa-8-azaspiro[4.5]decan-8-yl)-1-(4-fluorophenyl)butan-1-one
• CAS: 51787-84-9
• 化学式: C₁₇H₂₂FNO₃
• 分子量: 307.365
• InChiKey: WUERPSUXLDFSOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(1,4-dioxa-8-azaspiro<4.5>dec-8-yl)-4'-fluorobutyrophenone 在 三氟化硼乙醚 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 3.0h， 生成 1-<4,4-ethylenedithio-4-(4-fluorophenyl)butyl>-4-piperidinone
  参考文献：
  名称：

  Synthesis of Haloperidol Ethanedithioketal HIV-1 Protease Inhibitors: Magnesium Chloride Facilitated Addition of Grignard Reagents

  摘要：

  作为HIV-1蛋白酶抑制剂的有趣的羟哌啶酮酮缩醇和对苯二甲硫酮，通过将有机锂和有机镁试剂添加到已经含有酮缩醇或硫酮功能的酮前体来合成。向含有硫酮的酮中添加Grignard试剂的反应显著增强，而对含有酮缩醇的酮则适度增强，这是通过添加氯化镁实现的。氯化镁的影响归因于它竞争性地防止Grignard试剂的螯合和从4-氧哌啶环上的质子抽取。酮缩醇和硫酮的生物活性表明，硫酮功能比酮缩醇功能具有更强的抑制HIV-1蛋白酶的能力。

  DOI：

  10.1055/s-1993-25946
• 作为产物：
  描述：

  1,4-二氧杂-8-氮杂螺[4.5]癸烷-8-羧酸乙酯 在 氢氧化钾 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 4-(1,4-dioxa-8-azaspiro<4.5>dec-8-yl)-4'-fluorobutyrophenone
  参考文献：
  名称：

  Neurotropic and psychotropic agents. LXVII. 1-[4,4-Bis(4-fluorophenyl)butyl]-4-hydroxy-4-(3-trifluoromethyl-4-chlorophenyl)piperidine and related compounds: New synthetic approaches

  摘要：

  DOI：

  10.1135/cccc19733879

文献信息

• ¹⁸F-Labeled 1,4-Dioxa-8-azaspiro[4.5]decane Derivative: Synthesis and Biological Evaluation of a σ₁ Receptor Radioligand with Low Lipophilicity as Potent Tumor Imaging Agent
  作者：Fang Xie、Ralf Bergmann、Torsten Kniess、Winnie Deuther-Conrad、Constantin Mamat、Christin Neuber、Boli Liu、Jörg Steinbach、Peter Brust、Jens Pietzsch、Hongmei Jia

  DOI：10.1021/acs.jmedchem.5b00593

  日期：2015.7.23

  We report the syntheses and evaluation of series of novel piperidine compounds with low lipophilicity as σ1 receptor ligands. 8-(4-(2-Fluoroethoxy)benzyl)-1,4-dioxa-8-azaspiro[4.5]decane (5a) possessed high affinity (Ki = 5.4 ± 0.4 nM) for σ1 receptors and selectivity for σ2 receptors (30-fold) and the vesicular acetylcholine transporter (1404-fold). [18F]5a was prepared using a one-pot, two-step labeling

  我们报告低亲脂性系列新颖的哌啶化合物作为σ的合成和评价1受体配体。8-（4-（2-氟乙氧基）苄基）-1,4-二氧杂-8-氮杂螺[4.5]癸烷（5A）具有高亲和力（ķ我= 5.4±0.4纳米）为σ 1个受体和选择性σ 2受体（30倍）和水泡乙酰胆碱转运蛋白（1404倍）。[ 18 F] 5a是在自动合成模块中使用一锅，两步标记程序制备的，放射化学纯度> 95％，比活度为25-45 GBq /μmol。细胞结合，生物分布和放射自显影与阻断实验表明[18 F]图5a到σ 1种受体在体外和体内。使用小鼠肿瘤异种移植模型的小动物正电子发射断层扫描（PET）成像显示在人类癌和黑色素瘤中高积累。氟哌啶醇的治疗显着减少了放射性示踪剂在肿瘤中的积累。这些结果表明与合适的亲脂性和适当的亲合力放射性示踪剂为σ 1个受体可用于肿瘤成像。
• Spiro[1,2,4-benzotriazine-3(4H),4′-(1′-substituted)piperidines] and related compounds as ligands for sigma receptors
  作者：Federica Novelli、Fabio Sparatore

  DOI：10.1016/s0014-827x(02)01293-4

  日期：2002.11

  As analogues of some conformationally restricted spiropiperidine derivatives which are endowed with high affinity for sigma(1), receptor, a set of 16 spiro[1,2,4-benzotriazine-3(4H),4'-(1'-substituted)piperidines] and congeneric compounds was prepared and tested for affinity to a, receptor subtype. All N-arylalkyl substituted derivatives exhibited high affinity for the relevant receptor, with K-i in the low nanomolar range. Affinity for sigma(2) subtype (assayed only for a few representative compounds) was from one to three order of magnitude lower. Spiro[ 1,2,4-benzotriazine-3(4H),4'-(1'-benzyl)piperidine] (2), with a ratio K(i)sigma(2)/K(j)sigma(1) = 7000 should represent the most selective sigma(1), ligand so far described. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
• Bioisosteric Replacement Leading to Biologically Active [2.2]Paracyclophanes with Altered Binding Profiles for Aminergic G-Protein-Coupled Receptors
  作者：Marika Skultety、Harald Hübner、Stefan Löber、Peter Gmeiner

  DOI：10.1021/jm100899z

  日期：2010.10.14

  Exploring the chemical diversity space of GPCR ligands, we recently discovered [2.2]paracyclophanes as valuable atypical bioisosteres for secondary affinity and selectivity generating moieties. In find out if such an exchange also works for structural moieties that simulate the endogenous neurotransmitter, pi 1 or pi 2 or both systems pi 1 and pi 2 of three representative privileged structures of types 1, 2. and 3 were replaced by a [2.2]paracyclophane unit. Contributions of the respective functionalities to the binding at of a panel of relevant monoaminergic GPCRs were systematically examined. The study led to the paracyclophanylpiperazine 3a displaying excellent D-3 affinity (K-i = 1.6 nM) and a strongly attenuated binding to D-4, 5-HT1 and alpha(1). Whereas functional experiments showed neutral D-3 antagonist properties, mutagenesis studies indicated a binding mode that is similar to its lead compounds of type 3.
• Novelli; Sparatore, Il Farmaco, 1996, vol. 51, # 8-9, p. 541 - 550
  作者：Novelli、Sparatore

  DOI：——

  日期：——
• Sui Zhihua, De Voss James J., DeCamp Dianne L., Li Jia, Craik Charles S.,+, Synthesis, (1993) N 8, S 803- 808
  作者：Sui Zhihua, De Voss James J., DeCamp Dianne L., Li Jia, Craik Charles S.,+

  DOI：——

  日期：——