N-(4-aminophenethyl)-5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine | 136247-13-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: N-(4-aminophenethyl)-5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine
• 英文别名: N-[2-(4-aminophenyl)ethyl]-5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine
• CAS: 136247-13-7
• 化学式: C₂₂H₃₀N₂O
• 分子量: 338.493
• InChiKey: NQEBPWMALAKINE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  25.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  38.49
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-(4-aminophenethyl)-5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine 在 三溴化硼 、 potassium iodide 作用下， 以 二氯甲烷 、 正丁醇 为溶剂， 反应 2.0h， 生成 6-[2-[4-[(4-Nitro-2,1,3-benzoxadiazol-7-yl)amino]phenyl]ethyl-propylamino]-5,6,7,8-tetrahydronaphthalen-1-ol
  参考文献：
  名称：

  Fluorescent probes for dopamine receptors: synthesis and characterization of fluorescein and 7-nitrobenz-2-oxa-1,3-diazol-4-yl conjugates of D-1 and D-2 receptor ligands

  摘要：

  Fluorescent probes have been designed and developed for dopamine D-1 and D-2 receptors. Fluorescein and/or NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) derivatives of PPHT (D-2 agonist), spiperone (D-2 antagonist), SKF 38393 (D-1 agonist), and SKF 83566 (D-1 antagonist) were synthesized via their amino-functionalized analogues and all ligands were pharmacologically evaluated by measuring their ability to displace [H-3]SCH 23390 and [H-3]spiperone from D-1 and D-2 receptor sites in caudate putamen of monkeys (Macaca fascicularis). The fluorescein derivatives of PPHT and SKF 83566 and the NBD derivatives of spiperone and SKF 83566 retained the high affinity and selectivity of the parent ligands. The NBD derivatives of PPHT showed higher D-2 receptor affinity and selectivity than their parent ligands. The enantiomers of the fluorescent derivatives of PPHT were also synthesized and were found to exhibit stereoselectivity in binding to the D-2 receptor, with the S enantiomers having a considerably higher affinity than their R analogues. In contrast to these results, the fluorescein derivative of SKF 38393 showed only a low affinity for the D-1 receptor. These fluorescein- and NBD-coupled D-1 and D-2 receptor ligands have considerable significance as potential probes in the study of distribution of the receptors at the cellular/subcellular level and of their mobility in membranes in normal/diseased states by use of fluorescence microscopic and fluorescence photobleaching recovery techniques, respectively. The development of these novel fluorescent probes should also provide new leads for the design and synthesis of additional fluorescent ligands with better fluorescent properties and/or higher affinity/selectivity for the DA receptors.

  DOI：

  10.1021/jm00115a012
• 作为产物：
  描述：

  5-methoxy-N-(4-nitrophenethyl)-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine 在 肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以74%的产率得到N-(4-aminophenethyl)-5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine
  参考文献：
  名称：

  Adenosine A_2A Receptor-Antagonist/Dopamine D₂ Receptor-Agonist Bivalent Ligands as Pharmacological Tools to Detect A_2A-D₂ Receptor Heteromers

  摘要：

  Adenosine A(2A) (A(2A)R) and dopamine D-2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease. Here, a family of heterobivalent ligands containing a D,R agonist and an A2AR antagonist linked through a spacer of variable size was designed and synthesized to study A(2A)R-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A(2A)R with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A(2A)R-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A(2A)R-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy.

  DOI：

  10.1021/jm900298c

文献信息

• Design, Synthesis, and Biological Evaluation of Bivalent Ligands Targeting Dopamine D₂ -Like Receptors and the μ-Opioid Receptor
  作者：Mingcheng Qian、Lakshmi Vasudevan、Jelle Huysentruyt、Martijn D. P. Risseeuw、Christophe Stove、Patrick M. L. Vanderheyden、Kathleen Van Craenenbroeck、Serge Van Calenbergh

  DOI：10.1002/cmdc.201700787

  日期：2018.5.8

  This report describes the design and synthesis of novel heterobivalent ligands for dopamine D2‐like receptors (D2‐likeR) and the μ‐opioid receptor (μOR) and their evaluation using ligand binding and functional assays. Interestingly, we identified a potent bivalent ligand that contains a short 18‐atom linker and combines good potency with high efficacy both in β‐arrestin 2 recruitment for μOR and MAPK‐P

  当前，越来越多的证据表明分子间受体之间的相互作用可能会导致受体识别，药理学和信号传导发生改变。异二价配体已被证明可用于确认和靶向异聚受体的分子探针。本报告介绍了多巴胺D 2样受体（D 2 likeR）和μ阿片受体（μOR）的新型异二价配体的设计和合成，以及使用配体结合和功能测定进行的评估。有趣的是，我们确定了一种有效的二价配体，该配体包含一个短的18原子接头，并且在β-arrestin2募集μOR和MAPK-P募集D 4方面都具有良好的效能和高效能R.此外，该化合物的特征是D 4 R–μOR异二聚体的双相竞争结合曲线，表明是二价结合模式。由于该化合物可能桥接了D 4 R–μOR异二聚体，因此可以用作进一步研究D 4 R与μOR相互作用的药理学工具。