N-(7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-propionamide | 477788-86-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-propionamide
• 英文别名: 7-Methoxyl-2-[N-propionyl-(N-(4-phenylpiperazin-1-yl)-ethyl)amino]tetralin；N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-[2-(4-phenylpiperazin-1-yl)ethyl]propanamide
• CAS: 477788-86-6
• 化学式: C₂₆H₃₅N₃O₂
• 分子量: 421.583
• InChiKey: WKUHWWPRNMAMRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  36
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-propionamide 在 lithium aluminium tetrahydride 、 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 7-hydroxyl-2-[N-propyl-(N-(4-phenylpiperazin-1-yl)-ethyl)amino]tetralin
  参考文献：
  名称：

  Synthesis and biological characterization of novel hybrid 7-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol and their heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors

  摘要：

  In a recent preliminary communication we described the development of a series of hybrid molecules for the dopamine D2 and D3 receptor subtypes. The design of these compounds was based on combining pharmacophoric elements of aminotetralin and piperazine molecular fragments derived from known dopamine receptor agonist and antagonist molecules. Molecules developed from this approach exhibited high affinity and selectivity for the D3 receptor as judged from preliminary [H-3]spiperone binding data. In this report, we have expanded our previous finding by developing additional novel molecules and additionally evaluated functional activities of these novel molecules in the [H-3]thymidine incorporation mitogenesis assay. The binding results indicated highest selectivity in the bioisosteric benzothiazole derivative N6-[2-(4-phenyl-piperazin-1-yl)-ethyl]-N6-propyl-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine (14) for the D3 receptor whereas the racemic compound 7-({2-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-ethyl}-propyl-amino)-5,6,7,8-tetrahydro-naphthaten-2-ol (10c) showed the strongest potency. Mitogenesis studies to evaluate functional activity demonstrated potent agonist properties in these novel derivatives for both D2 and D3 receptors. In this regard, compound 7-{[4-(4-phenyl-piperazin-1-yl)-butyl]-prop-2-ynyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol (7b) exhibited the most potent agonist activity at the D3 receptor, 10 times more potent than quinpirole and was also the most selective compound for the D3 receptor in this series. Racemic compound 10a was resolved; however, little separation of activity was found between the two enantiomers of 10a. The marginally more active enantiomer (-)-10a was examined in vivo using the 6-OH-DA induced unilaterally lesioned rat model to evaluate its activity in producing contralateral rotations. The results demonstrated that in comparison to the reference compound apomorphine, (-)-10a was quite potent in inducing contralateral rotations and exhibited longer duration of action. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.019
• 作为产物：
  描述：

  2-(4-苯基-哌嗪-1-基)-乙胺 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 N-(7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-propionamide
  参考文献：
  名称：

  Synthesis and biological characterization of novel hybrid 7-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol and their heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors

  摘要：

  In a recent preliminary communication we described the development of a series of hybrid molecules for the dopamine D2 and D3 receptor subtypes. The design of these compounds was based on combining pharmacophoric elements of aminotetralin and piperazine molecular fragments derived from known dopamine receptor agonist and antagonist molecules. Molecules developed from this approach exhibited high affinity and selectivity for the D3 receptor as judged from preliminary [H-3]spiperone binding data. In this report, we have expanded our previous finding by developing additional novel molecules and additionally evaluated functional activities of these novel molecules in the [H-3]thymidine incorporation mitogenesis assay. The binding results indicated highest selectivity in the bioisosteric benzothiazole derivative N6-[2-(4-phenyl-piperazin-1-yl)-ethyl]-N6-propyl-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine (14) for the D3 receptor whereas the racemic compound 7-({2-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-ethyl}-propyl-amino)-5,6,7,8-tetrahydro-naphthaten-2-ol (10c) showed the strongest potency. Mitogenesis studies to evaluate functional activity demonstrated potent agonist properties in these novel derivatives for both D2 and D3 receptors. In this regard, compound 7-{[4-(4-phenyl-piperazin-1-yl)-butyl]-prop-2-ynyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol (7b) exhibited the most potent agonist activity at the D3 receptor, 10 times more potent than quinpirole and was also the most selective compound for the D3 receptor in this series. Racemic compound 10a was resolved; however, little separation of activity was found between the two enantiomers of 10a. The marginally more active enantiomer (-)-10a was examined in vivo using the 6-OH-DA induced unilaterally lesioned rat model to evaluate its activity in producing contralateral rotations. The results demonstrated that in comparison to the reference compound apomorphine, (-)-10a was quite potent in inducing contralateral rotations and exhibited longer duration of action. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.019

文献信息

• Hybrid 2-aminotetralin and aryl-substituted piperazine compounds and their use in altering cns activity
  申请人：——

  公开号：US20030195219A1

  公开（公告）日：2003-10-16

  Hybrid compounds containing in aminotetralin moiety or a heterocyclic and/or open chain analog thereof linked through an alkylene group to an aryl ring system-substituted piperidiene moiety exhibit high levels of CNS activity, in some cases exhibiting especially high relative binding efficiencies between D3 and D2 dopaminergic receptor subtypes.

  含有氨基四氢萘基团或其杂环和/或开链类似物的混合化合物，通过烷基基团连接到芳香环系统取代哌啶基团，表现出高水平的中枢神经系统活性，在某些情况下尤其表现出D3和D2多巴胺受体亚型之间的相对结合效率特别高。
• Hybrid 2-aminoterailin and aryl-substituted piperazine compounds and their use in altering CNS activity
  申请人：Dutta K. Aloke

  公开号：US20060020132A1

  公开（公告）日：2006-01-26

  Hybrid compounds containing an aminotetralin moiety or a heterocyclic and/or open chain analog thereof linked through an alkylene group to an aryl ring system-substituted piperidiene moiety exhibit high levels of CNS activity, in some cases exhibiting especially high relative binding efficiencies between D3 and D2 dopaminergic receptor subtypes.

  含有氨基四氢萘基团或杂环和/或开链类似物的混合化合物，通过烷基链连接到芳香环系统取代的哌啶基团，表现出高水平的中枢神经系统活性，在某些情况下表现出D3和D2多巴胺受体亚型之间特别高的相对结合效率。
• Hybrid 2-Aminotetralin and Aryl-Substituted Piperazine Compounds and their Use in Altering CNS Activity
  申请人：Dutta Aloke K.

  公开号：US20100210663A1

  公开（公告）日：2010-08-19

  Hybrid compounds containing an aminotetralin moiety or a heterocyclic and/or open chain analog thereof linked through an alkylene group to an aryl ring system-substituted piperidiene moiety exhibit high levels of CNS activity, in some cases exhibiting especially high relative binding efficiencies between D3 and D2 dopaminergic receptor subtypes.

  含有氨基四氢萘基团或其杂环和/或开链类似物的杂化化合物，通过烷基链连接到芳环系统取代的哌啶基团，表现出高水平的中枢神经系统活性，在某些情况下，表现出特别高的D3和D2多巴胺受体亚型之间相对结合效率。
• A novel series of hybrid compounds derived by combining 2-aminotetralin and piperazine fragments: binding activity at D2 and D3 receptors
  作者：Aloke K Dutta、Xiang-Shu Fei、Maarten E.A Reith

  DOI：10.1016/s0960-894x(01)00820-4

  日期：2002.2

  A series of 7-hydroxy-2-[N-alkyl-(N-(4-pheny1piperazine)-alkyl)amino]tetralins was developed based on a novel hybrid approach that combined 2-aminotetralin and arylpiperazine pharmacophoric moieties. Our preliminary study revealed that a four-methylene butyl linker produced very potent compounds for both the D-2 and D-3 receptors. Further structure-activity studies led to a novel template showing 50- to 100-fold selectivity for the D-3 receptor. (C) 2002 Elsevier Science Ltd. All rights reserved.
• US6982332B2
  申请人：——

  公开号：US6982332B2

  公开（公告）日：2006-01-03