N-(1-苯乙基-4-哌啶基)丙酰苯胺盐酸盐 | 1443-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: N-(1-苯乙基-4-哌啶基)丙酰苯胺盐酸盐
• 中文别名: 盐酸芬太尼
• 英文名称: fentanyl hydrochloride
• 英文别名: fentanyl HCl；hydron;N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide;chloride
• CAS: 1443-54-5
• 化学式: C₂₂H₂₈N₂O*ClH
• 分子量: 372.938
• InChiKey: LHCBOXPPRUIAQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.56
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  23.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  芬太尼 在 盐酸 作用下， 以 乙醚 、 水 为溶剂， 反应 2.0h， 以97%的产率得到N-(1-苯乙基-4-哌啶基)丙酰苯胺盐酸盐
  参考文献：
  名称：

  芬太尼和相关类似物的高效、优化合成。

  摘要：

  描述了母体阿片类芬太尼及其类似物的替代和优化合成。在对每个合成步骤进行优化研究后，所展示的路线表现出高产转化，导致这些强大的镇痛药。一般的三步策略以优异的产率 (73-78%) 产生了一组四种芬太尼，以及它们更常见的盐酸盐和柠檬酸盐。以下策略为克级、高效生产这一类有趣的阿片类生物碱提供了机会。

  DOI：

  10.1371/journal.pone.0108250

文献信息

• Metabolism of Fentanyl and Acetylfentanyl in Human-Induced Pluripotent Stem Cell-Derived Hepatocytes
  作者：Tatsuyuki Kanamori、Yuko Togawa Iwata、Hiroki Segawa、Tadashi Yamamuro、Kenji Kuwayama、Kenji Tsujikawa、Hiroyuki Inoue

  DOI：10.1248/bpb.b17-00709

  日期：——

  To evaluate the capability of human-induced pluripotent stem cell-derived hepatocytes (h-iPS-HEP) in drug metabolism, the profiles of the metabolites of fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of fentanyl, in the cells were determined and analyzed. Commercially available h-iPS-HEP were incubated with fentanyl or acetylfentanyl for 24 or 48 h. After enzymatic hydrolysis, the medium was deproteinized with acetonitrile, then analyzed by LC/MS. Desphenethylated metabolites and some hydroxylated metabolites, including 4′-hydroxy-fentanyl and β-hydroxy-fentanyl, were detected as metabolites of fentanyl and acetylfentanyl in the medium. The main metabolite of fentanyl with h-iPS-HEP was the desphenethylated metabolite, which was in agreement with in vivo results. These results suggest that h-iPS-HEP may be useful as a tool for investigating drug metabolism.

  为了评估人诱导多能干细胞衍生的肝细胞（h-iPS-HEP）在药物代谢中的能力，测定并分析了强效合成阿片类药物芬太尼和其N-乙酰化类似物乙酰芬太尼在细胞中的代谢物谱。将市售的h-iPS-HEP与芬太尼或乙酰芬太尼共同孵育24或48小时。通过酶解后，用乙腈去蛋白化处理介质，然后通过LC/MS进行分析。在介质中检测到去苯乙基代谢物和一些羟基化代谢物，包括4′-羟基芬太尼和β-羟基芬太尼，它们作为芬太尼和乙酰芬太尼的代谢物存在。与体内结果一致的是，h-iPS-HEP主要代谢芬太尼为去苯乙基代谢物。这些结果表明，h-iPS-HEP可能作为研究药物代谢的有用工具。
• [EN] INDUSTRIAL METHOD FOR SEPARATION AND PURIFICATION OF FENTANYL BY REVERSE PHASE PREPARATIVE CHROMATOGRAPHY<br/>[FR] PROCEDE INDUSTRIEL POUR SEPARER ET PURIFIER DU FENTANYLE PAR CHROMATOGRAPHIE PREPARATIVE A PHASE INVERSE
  申请人：MALLINCKRODT INC

  公开号：WO2005044798A1

  公开（公告）日：2005-05-19

  There is described a process for the purification of an impure preparation containing fentanyl by means of a reverse phase preparative chromatography process. A chromatographic column is loaded with a stationary phase, typically a silica particle having an organic ligand bound thereto. With a loading ratio of from about 50 to about 150 the impure preparation is acidified and passed through the column. The column is eluted with typically an aqueous solution of acetonitrile and the purified fentanyl is obtained in a specified cut.

  描述了一种通过反相制备色谱法净化含有芬太尼的不纯制剂的过程。色谱柱装有固定相，通常是带有有机配体的二氧化硅颗粒。将不纯制剂酸化后以约50至150的装载比例通过柱。通常用乙腈的水溶液洗脱柱，从而获得指定的芬太尼纯化产物。
• Evaluation of Agonistic Activity of Fluorinated and Nonfluorinated Fentanyl Analogs on μ-Opioid Receptor Using a Cell-Based Assay System
  作者：Tatsuyuki Kanamori、Yuki Okada、Hiroki Segawa、Tadashi Yamamuro、Kenji Kuwayama、Kenji Tsujikawa、Yuko Togawa Iwata

  DOI：10.1248/bpb.b20-00780

  日期：2021.2.1

  The agonistic activity of fluorinated and nonfluorinated fentanyl analogs on µ-opioid receptor was investigated using a cell-based assay system. Based on the activity, fentanyl analogs were ranked as follows: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanyl. However, among the fentanyl analogs fluorinated on the N-phenyl ring, 2-fluoro analogs and 3-fluoro analogs showed the strongest and weakest activities, respectively. These results suggest that the 2-fluorinated isomers of fentanyl analogs are more likely to cause poisoning.

  使用基于细胞的检测系统研究了含氟和不含氟的芬太尼类似物在μ-阿片受体上的拮抗活性。根据活性，芬太尼类似物的排名如下：芬太尼 > 异丁酰芬太尼 ≈ 丁酰芬太尼 ≈ 甲氧基乙酰芬太尼 > 乙酰芬太尼。然而，在N-苯环上含氟的芬太尼类似物中，2-氟类似物显示出最强活性，而3-氟类似物显示出最弱活性。这些结果表明，2-氟化的芬太尼类似物更可能导致中毒。
• Hyperpolarization of Pyridyl Fentalogues by Signal Amplification By Reversible Exchange (SABRE)
  作者：Thomas B. R. Robertson、Lysbeth H. Antonides、Nicolas Gilbert、Sophie L. Benjamin、Stuart K. Langley、Lindsey J. Munro、Oliver B. Sutcliffe、Ryan E. Mewis

  DOI：10.1002/open.201900273

  日期：2019.12

  laboratories produce analogues of fentanyl, known as fentalogues to circumvent legislation regarding its production. Three pyridyl fentalogues were synthesized and then hyperpolarized by signal amplification by reversible exchange (SABRE) to appraise the forensic potential of the technique. A maximum enhancement of ‐168‐fold at 1.4 T was recorded for the ortho pyridyl 1H nuclei. Studies of the activation parameters

  芬太尼，也被称为“困境”，是一种合成的阿片类药物，效力比吗啡高50-100倍。秘密实验室生产芬太尼的类似物，被称为fentalogues，以绕开有关其生产的立法。合成了三个吡啶基苯甲酸酯类化合物，然后通过可逆交换（SABRE）进行信号放大来超极化，以评估该技术的法医潜力。对于正吡啶基1 H核，在1.4 T时记录到最大168倍的增强。对于三个fentalogues激活参数的研究表明，配位体损失的比率反向氢化物和氢化物损失的配合物[Ir（IMES）（L）3（H）2 ] +（IMES = 1,3-双（2,4,6-三甲基苯基）咪唑-2-亚基）的范围为0.52至1.83。在地球磁场下进行SABRE之后，具有最接近于单位的比率的fentalogue产生了最大的增强作用。可以从主要由海洛因组成的基质（97：3海洛因：fentalogue）中选择性地使吡啶基苯妥英钠超极化，以验证SABER作为法医工具的用途。
• MODIFIED CYCLODEXTRINS FOR THE SELECTIVE SEQUESTRATION OF FENTANYL RELATED COMPOUNDS AND USES THEREOF
  申请人：LAWRENCE LIVERMORE NATIONAL SECURITY, LLC

  公开号：US20180371110A1

  公开（公告）日：2018-12-27

  Novel thioalkylcarboxylate-modified CDs and pharmaceutical compositions comprising these thioalkylcarboxylate-modified CDs are disclosed, as well as methods of using the disclosed thioalkylcarboxylate-modified CDs and pharmaceutical compositions thereof to neutralize or reduce undesired effects or symptoms associated with one or more fentanyl related compounds in a subject in need thereof. The use of the disclosed thioalkylcarboxylate-modified CDs to detect the presence of one or more fentanyl related compounds in a sample is also disclosed, which comprises contacting the sample with said thioalkylcarboxylate-modified CDs or a composition comprising these CDs.

  揭示了新型硫代烷基羧酸酯修饰的CDs以及包括这些硫代烷基羧酸酯修饰的CDs的药物组合物，以及使用所述的硫代烷基羧酸酯修饰的CDs和这些药物组合物来中和或减少与一种或多种芬太尼相关化合物在需要的受试者中相关的不良效应或症状的方法。还揭示了使用所述的硫代烷基羧酸酯修饰的CDs来检测样品中一种或多种芬太尼相关化合物的存在，其中包括将样品与所述的硫代烷基羧酸酯修饰的CDs或包含这些CDs的组合物接触。