Butyrfentanyl hydrochloride | 1443-52-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: Butyrfentanyl hydrochloride
• 英文别名: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]butanamide;hydrochloride
• CAS: 1443-52-3
• 化学式: C₂₃H₃₀N₂O*(x)ClH
• 分子量: 387.0
• InChiKey: OHCXSXCINRZXIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.95
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 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：

  N-(1-phenethylpiperidin-4-ylidene)aniline 在 盐酸 、 sodium tetrahydroborate 作用下， 生成 Butyrfentanyl hydrochloride
  参考文献：
  名称：

  Evaluation of Agonistic Activity of Fluorinated and Nonfluorinated Fentanyl Analogs on μ-Opioid Receptor Using a Cell-Based Assay System

  摘要：

  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。

  DOI：

  10.1248/bpb.b20-00780

文献信息

• Metabolism of Butyrylfentanyl in Fresh Human Hepatocytes: Chemical Synthesis of Authentic Metabolite Standards for Definitive Identification
  作者：Tatsuyuki Kanamori、Yuko Togawa Iwata、Hiroki Segawa、Tadashi Yamamuro、Kenji Kuwayama、Kenji Tsujikawa、Hiroyuki Inoue

  DOI：10.1248/bpb.b18-00765

  日期：2019.4.1

  The metabolism of butyrylfentanyl, a new designer drug, was investigated using fresh human hepatocytes isolated from a liver-humanized mouse model. In the culture medium of hepatocytes incubated with butyrylfentanyl, the desphenethylated metabolite (nor-butyrylfentanyl), ω-hydroxy-butyrylfentanyl, (ω-1)-hydroxy-butyrylfentanyl, 4′-hydroxy-butyrylfentanyl, β-hydroxy-butyrylfentanyl, 4′-hydroxy-3′-methoxy-butyrylfentanyl, and ω-carboxy-fentanyl were identified as the metabolites of butyrylfentanyl. Each metabolite was definitively identified by comparing the analytical data with those of authentic standards. The amount of the main metabolite, nor-butyrylfentanyl, reached 37% of the initial amount of butyrylfentanyl at 48 h. ω-Hydroxy-butyrylfentanyl and (ω-1)-hydroxy-butyrylfentanyl, formed by hydroxylation at the N-butyryl group of butyrylfentanyl, were the second and third largest metabolites, respectively. The majority of 4′-hydroxy-butyrylfentanyl and 4′-hydroxy-3′-methoxy-butyrylfentanyl was considered to be conjugated. CYP reaction phenotyping for butyrylfentanyl using human liver microsomes and various anti-CYP antibodies revealed that CYP3A4 was involved in the formation of nor-butyrylfentanyl, (ω-1)-hydroxy-butyrylfentanyl, and β-hydroxy-butyrylfentanyl. In contrast, CYP2D6 was involved in the formation of ω-hydroxy-butyrylfentanyl.

  使用从肝人源化小鼠模型中分离的新鲜人肝细胞，研究了一种新型设计药物丁酰芬太尼的代谢情况。在与人肝细胞共培养的介质中，鉴定出了丁酰芬太尼的脱芬太尼代谢物（去甲丁酰芬太尼）、ω-羟基丁酰芬太尼、(ω-1)-羟基丁酰芬太尼、4′-羟基丁酰芬太尼、β-羟基丁酰芬太尼、4′-羟基-3′-甲氧基丁酰芬太尼和ω-羧基芬太尼作为其代谢物。每个代谢物通过与标准品的分析数据比较得到确切鉴定。主要代谢物去甲丁酰芬太尼的量在48小时达到了初始丁酰芬太尼量的37%。由丁酰芬太尼的N-丁酰基团羟化形成的ω-羟基丁酰芬太尼和(ω-1)-羟基丁酰芬太尼分别为第二和第三大代谢物。大多数4′-羟基丁酰芬太尼和4′-羟基-3′-甲氧基丁酰芬太尼被认为是共轭物。使用人肝微粒体和各种抗CYP抗体对丁酰芬太尼进行CYP反应表型分析显示，CYP3A4参与了去甲丁酰芬太尼、(ω-1)-羟基丁酰芬太尼和β-羟基丁酰芬太尼的形成。相比之下，CYP2D6参与了ω-羟基丁酰芬太尼的形成。
• 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。