阿扎哌醇 | 2804-05-9

• 物质功能分类: 分析化学 - 标准品 - 分析标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 阿扎哌醇
• 英文名称: (R)-(+)-α-(4-fluorophenyl)-4-(2-pyridinyl)-1-piperazinebutanol
• 英文别名: Azaperol；1-(4-fluorophenyl)-4-(4-pyridin-2-ylpiperazin-1-yl)butan-1-ol
• CAS: 2804-05-9
• 化学式: C₁₉H₂₄FN₃O
• 分子量: 329.417
• InChiKey: LVXYAFNPMXCRJI-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）
• 碰撞截面：
  191.54 Ų [M-H]-; 182.91 Ų [M+H]+

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  39.6
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S20,S6,S62
• 危险类别码：
  R22
• 海关编码：
  29335990
• WGK Germany：
  3

制备方法与用途

阿扎哌醇又叫氮哌醇，是氮哌酮的代谢物。氮哌酮（Azaperone）是一种丁酰苯类神经松弛剂，肌肉注射后可使动物产生精神性运动镇静作用，从而使动物变得安静并对环境淡漠。

反应信息

• 作为反应物：
  描述：

  阿扎哌醇 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 0.5h， 以99%的产率得到1-(4-fluorophenyl)-4-<4-(5-bromo-2-pyridinyl)-1-piperazinyl>-1-butanol
  参考文献：
  名称：

  Identification of Metabolites of Azaperone in Horse Urineǁ⊥

  摘要：

  Two metabolites of the tranquilizer azaperone were extracted from alkalinized horse urine after treatment with beta-glucuronidase/sulfatase from limpets (Patella vulgata). The metabolites were identified by a combination of independent chemical synthesis and GC/MS and H-1 NMR analysis. The metabolites were identified as 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1-piperazinyl]-1 -butanol, designated as 5'-hydroxyazaperol, and 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1 -piperazinyl]-1-butanone, designated as 5'-hydroxyazaperone. A TLC screening test was developed for detecting both metabolites in basic extracts of horse urine treated with beta-glucuronidase/sulfatase. The screening test was used to detect azaperone metabolites in extracts of horse urine collected for 24 h after intravenous administration of azaperone. The administration of azaperone to horses was confirmed by GC/MS identification of 5'-hydroxyazaperone and 5'-hydroxyazaperol from basic extracts of horse urine treated with beta-glucuronidaseisulfatase. The extracted metabolites were treated with bis(trimethylsilyl)acetamide to produce trimethylsilyl (TMS) ether derivatives, and mass spectra and retention times were compared to those of the synthesized metabolites treated in the same manner.

  DOI：

  10.1021/js950205j
• 作为产物：
  描述：

  阿扎哌隆 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.5h， 以92%的产率得到阿扎哌醇
  参考文献：
  名称：

  Identification of Metabolites of Azaperone in Horse Urineǁ⊥

  摘要：

  Two metabolites of the tranquilizer azaperone were extracted from alkalinized horse urine after treatment with beta-glucuronidase/sulfatase from limpets (Patella vulgata). The metabolites were identified by a combination of independent chemical synthesis and GC/MS and H-1 NMR analysis. The metabolites were identified as 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1-piperazinyl]-1 -butanol, designated as 5'-hydroxyazaperol, and 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1 -piperazinyl]-1-butanone, designated as 5'-hydroxyazaperone. A TLC screening test was developed for detecting both metabolites in basic extracts of horse urine treated with beta-glucuronidase/sulfatase. The screening test was used to detect azaperone metabolites in extracts of horse urine collected for 24 h after intravenous administration of azaperone. The administration of azaperone to horses was confirmed by GC/MS identification of 5'-hydroxyazaperone and 5'-hydroxyazaperol from basic extracts of horse urine treated with beta-glucuronidaseisulfatase. The extracted metabolites were treated with bis(trimethylsilyl)acetamide to produce trimethylsilyl (TMS) ether derivatives, and mass spectra and retention times were compared to those of the synthesized metabolites treated in the same manner.

  DOI：

  10.1021/js950205j

文献信息

• Evaluation of the effects of the enantiomers of reduced haloperidol, azaperol, and related 4-amino-1-arylbutanols on dopamine and .sigma. receptors
  作者：Juan C. Jaen、Bradley W. Caprathe、Thomas A. Pugsley、Lawrence D. Wise、Hyacinth Akunne

  DOI：10.1021/jm00076a022

  日期：1993.11

  The enantiomers of reduced haloperidol (3a), azaperol (3b), and the related compound BMY-14802 (3c) were prepared in high optical purity. The affinity of these compounds for dopamine D2 and D3 receptors, and sigma S1 and S2 sites was determined in vitro. Both enantiomers of 3a display greatly decreased affinity for D2 and D3 receptors compared to haloperidol, although they still possess affinities in the 100-200-nM range. Both enantiomers of 3a possess potent and equal affinity for S1 sites (K-i: 1-2 nM), only slightly weaker than haloperidol (K-i: 0.33 nM). At S2 sites, (R)-(+)-3a displays similar affinity to haloperidol (K-i: 31 and 26 nM, respectively), while (S)-(-)-3a is slight more potent (K-i: 8.2 nM). The stereoselectivity profile of the enantiomers of 3b at D2 and D3 receptors is quite similar to that of 3a, (S)-(-)-3b being about 4 times more potent than its enantiomer at both receptors. (R)-(+)-3b binds preferentially to sigma S1 over S2 sites, while (S)-(-)-3b displays the opposite selectivity profile. Both enantiomers of 3c possess very weak affinity for D2 and D3 receptors. In a manner similar to the enantiomers of 3b, the affinity of (R)-(+)-3c is greater for S1 than S2 sites, while (S)-(-)-3c displays the opposite selectivity profile. Following parenteral administration of both enantiomers of 3a, dopamine synthesis and turnover in rat striatum, cortex, and mesolimbic areas were increased, in a manner similar to the effects produced by haloperidol itself. Additional studies will be required to assess with certainty whether the effects were due to the compounds themselves or simply were a consequence of the in vivo oxidation to haloperidol.
• 5 HT RECEPTOR MEDIATED NEUROGENESIS
  申请人：Barlow Carrolee

  公开号：US20100009983A1

  公开（公告）日：2010-01-14

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on use of a 5HTR agent, in combination with one or more other neurogenic agents, or anti-astrogenic agent, to stimulate or activate the formation of new nerve cells.
• Identification of Metabolites of Azaperone in Horse Urineǁ⊥
  作者：Richard A. Sams、Diane F. Gerken、Randall L. Detra、Scott D. Stanley、William E. Wood、Thomas Tobin、Jyan-Ming Yang、Hsin-Hsinng Tai、Alwarsamy Jegananthan、David S. Watt

  DOI：10.1021/js950205j

  日期：1996.1

  Two metabolites of the tranquilizer azaperone were extracted from alkalinized horse urine after treatment with beta-glucuronidase/sulfatase from limpets (Patella vulgata). The metabolites were identified by a combination of independent chemical synthesis and GC/MS and H-1 NMR analysis. The metabolites were identified as 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1-piperazinyl]-1 -butanol, designated as 5'-hydroxyazaperol, and 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1 -piperazinyl]-1-butanone, designated as 5'-hydroxyazaperone. A TLC screening test was developed for detecting both metabolites in basic extracts of horse urine treated with beta-glucuronidase/sulfatase. The screening test was used to detect azaperone metabolites in extracts of horse urine collected for 24 h after intravenous administration of azaperone. The administration of azaperone to horses was confirmed by GC/MS identification of 5'-hydroxyazaperone and 5'-hydroxyazaperol from basic extracts of horse urine treated with beta-glucuronidaseisulfatase. The extracted metabolites were treated with bis(trimethylsilyl)acetamide to produce trimethylsilyl (TMS) ether derivatives, and mass spectra and retention times were compared to those of the synthesized metabolites treated in the same manner.