1-<4-(4-fluorophenyl)-4,4-(ethylenedioxy)butyl>-4-piperidinone | 56660-98-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-<4-(4-fluorophenyl)-4,4-(ethylenedioxy)butyl>-4-piperidinone
• 英文别名: 1-<4,4-ethylenedioxy-4-(4-fluorophenyl)butyl>-4-piperidinone；1-<4-(4-fluorophenyl)-4,4-(ethylenedioxy)butyl>-4-piperidone；1-{3-[2-(4-fluoro-phenyl)-[1,3]dioxolan-2-yl]-propyl}-piperidin-4-one；1-(3-<2-(4-Fluorphenyl)-1,3-dioxolan-2-yl>-propyl)-4-piperidon；4-Piperidinone, 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-；1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]piperidin-4-one
• CAS: 56660-98-1
• 化学式: C₁₇H₂₂FNO₃
• 分子量: 307.365
• InChiKey: RAVDTDUTJJIOFY-UHFFFAOYSA-N

物化性质

• 熔点：
  57-60 °C
• 沸点：
  431.8±45.0 °C(Predicted)
• 密度：
  1.174±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：

  1-<4-(4-fluorophenyl)-4,4-(ethylenedioxy)butyl>-4-piperidinone 在 硫酸 、 氯化铵 作用下， 以 水 为溶剂， 反应 61.17h， 生成 1-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-4-methylamino-piperidine-4-carboxylic acid amide
  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：

  1-(4-(4-氟苯基)-4,4-(亚乙二氧基)丁基)-4-羟基哌啶 在 9-fluorene 、 potassium tert-butylate 作用下， 以 苯 为溶剂， 反应 2.5h， 以50%的产率得到1-<4-(4-fluorophenyl)-4,4-(ethylenedioxy)butyl>-4-piperidinone
  参考文献：
  名称：

  [82Br]溴哌啶的合成及在大鼠中的初步组织分布研究。

  摘要：

  描述了一种制备比活性为440μCi/ mg的[82Br]溴哌醇的方法。在合成路线的最后一步中，通过Brackman和Smit对Sandmeyer反应的修饰实现了将溴82掺入分子中。这涉及在乙腈中在Cu82Br2和一氧化氮气体之间形成配合物，然后使其与4- [4-（氨基苯基）-4-羟基-哌啶基] -1-（4-氟苯基）-1-丁酮反应（氨基哌啶醇，10）在约1.5小时内得到[82Br]溴哌醇。由K82Br和CuSO4.5H2O原位制备溴化铜82Br]。由K82Br制备[82Br]溴哌醇的放射化学和化学收率分别为10.4和12％。

  DOI：

  10.1021/jm00175a014

文献信息

• Synthesis of Haloperidol Ethanedithioketal HIV-1 Protease Inhibitors: Magnesium Chloride Facilitated Addition of Grignard Reagents
  作者：Zhihua Sui、James J. De Voss、Dianne L. Decamp、Jia Li、Charles S. Craik、Paul R. Ortiz de Montellano

  DOI：10.1055/s-1993-25946

  日期：——

  Haloperidol ketals and ethanedithioketals of interest as HIV-1 protease inhibitors were synthesized by addition of organolithium and organomagnesium reagents to ketone precursors already containing the ketal or thioketal functionality. Addition of Grignard reagents to the thioketal containing ketone was enhanced remarkably, and to the ketal containing ketone moderately, by the addition of magnesium chloride. The effect of magnesium chloride is attributed to its ability to competitively prevent chelation of the Grignard reagent and proton abstraction from the 4-oxopiperidine ring. The biological activities of the ketals and thioketals indicate that the thioketal function conveys greater ability to inhibit the HIV-1 protease than the ketal function.

  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。
• Rearrangement of spiro-benzimidazolines: preparation of N-alkenyl- and N-alkyl-benzimidazol-2-ones
  作者：Jeffrey T. Kuethe、Jack Varon、Karla G. Childers

  DOI：10.1016/j.tet.2007.06.106

  日期：2007.11

  A synthetically useful protocol has been developed for the preparation of highly functionalized N-alkenyl-benzimidazol-2-ones. Reaction of commercially available o-phenylenediamines with variously substituted cyclic ketones provides spiro-benzimidazolines. Treatment of these spiro-benzimidazolines with triphosgene in the presence of potassium carbonate results in rapid rearrangement and formation of N-alkenyl-benzimidazol-2-ones in modest to excellent yield for the two-step sequence. Extension of this methodology toward the preparation of a m opiate receptor antagonist and droperidol, a potent antiemetic and antipsychotic agent, currently a marketed pharmaceutical is also described. Upon treatment of spiro-benzimidazolines with triphosgene in the presence of sodium triacetoxyborohydride, N-alkyl-benzimidazol-2-ones were formed. (C) 2007 Merck & Co., Inc. Published by Elsevier Ltd. All rights reserved.
• FELLOWS I.; HARROW T. A.; HONEYMAN R., J. LABELLED COMPOUNDS AND RADIOPHARM., 1979, 16, NO 3, 449-461
  作者：FELLOWS I.、 HARROW T. A.、 HONEYMAN R.

  DOI：——

  日期：——
• Synthesis of [82Br]bromperidol and preliminary tissue distribution studies in the rat
  作者：Styliani H. Vincent、Manvendra B. Shambhu、George A. Digenis

  DOI：10.1021/jm00175a014

  日期：1980.1

  A procedure is described for the preparation of [82Br]bromperidol with specific activity 440 muCi/mg. The incorporation of bromine-82 into the molecule was accomplished through Brackman and Smit's modification of the Sandmeyer reaction, during the last step of the synthetic route. This involved the formation of a complex between Cu82Br2 and nitric oxide gas in acetonitrile, which was then allowed to

  描述了一种制备比活性为440μCi/ mg的[82Br]溴哌醇的方法。在合成路线的最后一步中，通过Brackman和Smit对Sandmeyer反应的修饰实现了将溴82掺入分子中。这涉及在乙腈中在Cu82Br2和一氧化氮气体之间形成配合物，然后使其与4- [4-（氨基苯基）-4-羟基-哌啶基] -1-（4-氟苯基）-1-丁酮反应（氨基哌啶醇，10）在约1.5小时内得到[82Br]溴哌醇。由K82Br和CuSO4.5H2O原位制备溴化铜82Br]。由K82Br制备[82Br]溴哌醇的放射化学和化学收率分别为10.4和12％。
• 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.