N-苯基-1-(2-苯乙基)-4-哌啶胺 | 21409-26-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-苯基-1-(2-苯乙基)-4-哌啶胺
• 中文别名: 4-苯基氨基-1-苯乙基哌啶；4-苯胺基-N-苯乙基哌啶；(1-苯乙基-哌啶-4-基)-苯基-胺
• 英文名称: (1-Phenethyl-piperidin-4-yl)-phenyl-amine
• 英文别名: N-[1-(2-phenylethyl)-4-piperidinyl]aniline；1-phenethyl-N-phenylpiperidin-4-amine；N-phenyl-1-(2-phenylethyl)piperidin-4-amine
• CAS: 21409-26-7
• 化学式: C₁₉H₂₄N₂
• 分子量: 280.413
• InChiKey: ZCMDXDQUYIWEKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-苯基-1-(2-苯乙基)-4-哌啶胺 在 盐酸 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 以95%的产率得到N-[1-(2-phenylethyl)-piperidin-4-yl]-nitrosoaniline
  参考文献：
  名称：

  Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain

  摘要：

  Acids 9a-f as possible bivalent ligands designed as a structural combination of opioid mu-agonist (Fentanyl) and NSAID ( Indomethacin) activities and produced compounds which were tested as analgesics. The obtained series of compounds exhibits low affinity and activity both at opioid receptors and as cyclooxygenase ( COX) inhibitors. One explanation of the weak opioid activity could be stereochemical peculiarities of these bivalent compounds which differ significantly from the fentanyl skeleton. The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.065
• 作为产物：
  描述：

  芬太尼 在 盐酸 、 水 、 ammonium hydroxide 作用下， 反应 72.0h， 以55.9%的产率得到N-苯基-1-(2-苯乙基)-4-哌啶胺
  参考文献：
  名称：

  多级质谱和氘标记法在芬太尼电喷雾电离质谱中鉴定等压产物离子

  摘要：

  尽管在某些情况下氘标记可以提供有用的结构信息来鉴定同量离子，但同量异位离子无法通过精确的质量测定加以区分。通过电喷雾电离离子阱质谱联用氘标记实验和区域特异性氘标记类似物的光谱，研究了芬太尼拟议的裂解途径。在串联质谱（MS / MS）条件下（m / z 188）芬太尼的主要产物离子是由N-苯基丙酰胺的中性损失引起的。有人提出将1-（2-苯基乙基）-1,2,3,6-四氢吡啶（1）作为产物离子的结构。但是，芬太尼m / z的进一步裂解（MS 3）188离子产生的产物离子与合成1的MS / MS片段中的产物离子不同，表明芬太尼的m / z 188产物离子具有与1的结构不同的同量异位结构。氧化氘中的一个等压线将其中一个等压线的质量提高了1 Da，而另一个等压线的质量保持不变。来自氘标记的提议的等压结构的多级质谱数据为两条裂解途径提供了支持。结果表明，多级质谱和氘标记在等压产物离子的结构分配中的实用性。版权所有©2010

  DOI：

  10.1002/rcm.4673
• 作为试剂：
  描述：

  N-(2-苯乙基)-4-哌啶酮 、 苯胺 、 三乙酰氧基硼氢化钠 在 N-苯基-1-(2-苯乙基)-4-哌啶胺 作用下， 以 溶剂黄146 为溶剂， 以The title compound was obtained as a white solid (74% yield)的产率得到N-苯基-1-(2-苯乙基)-4-哌啶胺
  参考文献：
  名称：

  Method and kit for detecting, or determining the quantity of, metabolites of fentanyl and metabolites of fentanyl analogs

  摘要：

  本发明提供了一种免疫原，包括将半抗原偶联到具有抗原性的载体材料上，以及包括上述半抗原偶联到标记试剂上的结合物，以及对上述免疫原进行提高的能够与芬太尼代谢产物和芬太尼类似物代谢产物的至少一个结构表位结合的抗体。

  公开号：

  US07109310B2

文献信息

• Chemoselective Reductive Aminations in Aqueous Nanoreactors Using Parts per Million Level Pd/C Catalysis
  作者：Ruchita R. Thakore、Balaram S. Takale、Gianluca Casotti、Eugene S. Gao、Henry S. Jin、Bruce H. Lipshutz

  DOI：10.1021/acs.orglett.0c02156

  日期：2020.8.21

  water between aldehydes or ketones and amines occurs smoothly within the hydrophobic cores of nanomicelles, resulting in imine formation that is subject to subsequent reduction leading, overall, to reductive amination. This micellar technology enables the synthesis of several types of pharmaceuticals, a new procedure that relies on only 2000 ppm (0.20 mol %) palladium from commercially available Pd/C. A

  醛或酮和胺之间的可循环水中冷凝在纳米胶束的疏水核内平稳进行，导致亚胺形成，该亚胺形成随后进行还原，总体上导致还原胺化。这种胶束技术能够合成多种类型的药物，这一新程序仅依赖于来自可商购Pd / C的2000 ppm（0.20 mol％）钯。在温和的条件下可以使用各种各样的底物，从而导致所需仲胺和叔胺的化学产率高。
• 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。
• 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。
• Palladium-catalyzed hydroaminocarbonylation of alkenes with amines promoted by weak acid
  作者：Guoying Zhang、Xiaolei Ji、Hui Yu、Lei Yang、Peng Jiao、Hanmin Huang

  DOI：10.1016/j.tetlet.2015.12.031

  日期：2016.1

  The weak acid has been identified as an efficient basicity-mask to overcome the basicity barrier imparted by aliphatic amines in the Pd-catalyzed hydroaminocarbonylation, which enables both aromatic and aliphatic amines to be applicable in the palladium-catalyzed hydroaminocarbonylation reaction. Notably, by using this protocol, the marketed herbicide of Propanil and drug of Fentanyl could be easily

  弱酸已被认为是一种有效的碱性掩盖剂，可以克服脂肪族胺在Pd催化的氢氨基羰基化反应中所赋予的碱性障碍，从而使芳香族胺和脂肪族胺均适用于钯催化的氢氨基羰基化反应。值得注意的是，通过使用该方案，可以容易地以一锅的方式获得市售的丙酸的除草剂和芬太尼的药物。
• N-aryl-N-(4-piperidinyl)amides and pharmaceutical compositions and
  申请人：The BOC Group, Inc.

  公开号：US04584303A1

  公开（公告）日：1986-04-22

  Compounds are disclosed of the formula ##STR1## optically active isomeric forms thereof, and/or pharmaceutically acceptable acid addition salts thereof, in which formula: R is defined in the disclosure.

  揭示了化合物的公式##STR1##及其光学活性异构体形式，和/或药用可接受的酸盐，其中公式中：R在披露中定义。