2-[N-phenylethyl-N-propyl]amino-5-hydroxytetralin | 129298-03-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 2-[N-phenylethyl-N-propyl]amino-5-hydroxytetralin
• 英文别名: (RS)-2--5-hydroxytetralin；6-((4-aminophenethyl)(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol；6-[2-(4-Aminophenyl)ethyl-propylamino]-5,6,7,8-tetrahydronaphthalen-1-ol
• CAS: 129298-03-9
• 化学式: C₂₁H₂₈N₂O
• 分子量: 324.466
• InChiKey: SPMVURQMVHUPOT-UHFFFAOYSA-N

物化性质

• 沸点：
  517.4±50.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异硫氰酸荧光素酯 、 2-[N-phenylethyl-N-propyl]amino-5-hydroxytetralin 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以56%的产率得到1-(3',6'-Dihydroxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-yl)-3-[4-[2-[(5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-propylamino]ethyl]phenyl]thiourea
  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：

  N-(4-aminophenethyl)-5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到2-[N-phenylethyl-N-propyl]amino-5-hydroxytetralin
  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

• N-[Chloro(dimethylamino)methylene]-N-methylmethanaminium chloride (TMUCl Cl), the reagent of choice for the solid-phase synthesis of anilides
  作者：Marc Vendrell、Rubén Ventura、Ariel Ewenson、Miriam Royo、Fernando Albericio

  DOI：10.1016/j.tetlet.2005.05.140

  日期：2005.8

  An effective solid-phase preparation of anilides from supported carboxylic acids is described by their activation as the corresponding acid chlorides with TMUCI Cl. (c) 2005 Elsevier Ltd. All rights reserved.
• Adenosine A_2A Receptor-Antagonist/Dopamine D₂ Receptor-Agonist Bivalent Ligands as Pharmacological Tools to Detect A_2A-D₂ Receptor Heteromers
  作者：Aroa Soriano、Ruben Ventura、Anabel Molero、Rob Hoen、Vicent Casadó、Antoni Cortés、Francesca Fanelli、Fernando Albericio、Carmen Lluís、Rafael Franco、Miriam Royo

  DOI：10.1021/jm900298c

  日期：2009.9.24

  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.
• 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
  作者：Venkatesalu Bakthavachalam、Nandkishore Baindur、Bertha K. Madras、John L. Neumeyer

  DOI：10.1021/jm00115a012

  日期：1991.11

  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.