N2-[2-(4-phenylpiperazin-1-yl)ethyl]-N2-propyl-1,2,3,4-tetrahydronaphthalene-2,7-diamine | 1003565-44-3

• 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: N2-[2-(4-phenylpiperazin-1-yl)ethyl]-N2-propyl-1,2,3,4-tetrahydronaphthalene-2,7-diamine
• 英文别名: 2-N-[2-(4-phenylpiperazin-1-yl)ethyl]-2-N-propyl-1,2,3,4-tetrahydronaphthalene-2,7-diamine
• CAS: 1003565-44-3
• 化学式: C₂₅H₃₆N₄
• 分子量: 392.588
• InChiKey: FJXRWQLSUYHSFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  35.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N2-[2-(4-phenylpiperazin-1-yl)ethyl]-N2-propyl-1,2,3,4-tetrahydronaphthalene-2,7-diamine 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 96.0h， 生成 2,2,2-trifluoro-1-(7-((2-(4-phenylpiperazin-1-yl)ethyl)(propyl)amino)-5,6,7,8-tetrahydro-1H-benzo[f]indol-1-yl)ethanone
  参考文献：
  名称：

  Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors

  摘要：

  The goal of the present study was to explore, in our previously developed hybrid template, the effect of introduction of additional heterocyclic rings (mimicking catechol hydroxyl groups as bioisosteric replacement) on selectivity and affinity for the D-3 versus D-2 receptor. In addition, we wanted to explore the effect of derivatization of functional groups of the agonist binding moiety in compounds developed by us earlier from the hybrid template. Binding affinity (K-i) of the new compounds was measured with tritiated spiperone as the radioligand and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed in the GTP gamma S binding assay. In the imidazole series, compound 10a exhibited the highest D-3 affinity whereas the indole derivative 13 exhibited similar high D-3 affinity. Functionalization of the amino group in agonist (+)-9d with different sulfonamides derivatives improved the D-3 affinity significantly with (+)-14f exhibiting the highest affinity. However, functionalization of the hydroxyl and amino groups of 15 and (+)-9d, known agonist and partial agonist, to sulfonate ester and amide in general modulated the affinity. In both cases loss of agonist potency resulted from such derivatization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.059
• 作为产物：
  描述：

  2-(R,S)-丙基氨基-1,2,3,4-四氢萘 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， -50.0~20.0 ℃ 、482.64 kPa 条件下， 反应 66.0h， 生成 N2-[2-(4-phenylpiperazin-1-yl)ethyl]-N2-propyl-1,2,3,4-tetrahydronaphthalene-2,7-diamine
  参考文献：
  名称：

  Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors

  摘要：

  The goal of the present study was to explore, in our previously developed hybrid template, the effect of introduction of additional heterocyclic rings (mimicking catechol hydroxyl groups as bioisosteric replacement) on selectivity and affinity for the D-3 versus D-2 receptor. In addition, we wanted to explore the effect of derivatization of functional groups of the agonist binding moiety in compounds developed by us earlier from the hybrid template. Binding affinity (K-i) of the new compounds was measured with tritiated spiperone as the radioligand and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed in the GTP gamma S binding assay. In the imidazole series, compound 10a exhibited the highest D-3 affinity whereas the indole derivative 13 exhibited similar high D-3 affinity. Functionalization of the amino group in agonist (+)-9d with different sulfonamides derivatives improved the D-3 affinity significantly with (+)-14f exhibiting the highest affinity. However, functionalization of the hydroxyl and amino groups of 15 and (+)-9d, known agonist and partial agonist, to sulfonate ester and amide in general modulated the affinity. In both cases loss of agonist potency resulted from such derivatization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.059

文献信息

• Further Structure–Activity Relationships Study of Hybrid 7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol Analogues: Identification of a High-Affinity D3-Preferring Agonist with Potent in Vivo Activity with Long Duration of Action
  作者：Swati Biswas、Suhong Zhang、Fernando Fernandez、Balaram Ghosh、Juan Zhen、Eldo Kuzhikandathil、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/jm070860r

  日期：2008.1.1

  (+)-isomeric counterpart. Binding results indicated highest selectivity for D3 receptors in compound (-)- 10 ( K i = 0.35 nM; D2/D3 = 71). In the 5-hydroxy series, highest selectivity for D3 receptors was exhibited by compound (-)- 25 ( K i = 0.82 nM; D2/D3 = 31.5). Most potent compounds exhibited binding and functional affinities at the sub-nanomolar level for the D3 receptor. Binding assays were carried

  本文介绍了一种针对多巴胺D2 / D3受体的氨基四氢萘-哌嗪类杂合分子的扩展结构-活性关系研究。已经开发出各种类似的作为位置异构体的类似物，其中酚羟基在芳族环上的位置已经改变。在两个邻苯二酚衍生物之间，具有两个亚甲基接头长度的化合物6e相对于具有四个亚甲基接头的化合物6f对D3的表现出更高的亲和力和对D3的选择性（6e和6f分别为D2 / D3 = 50.6 vs 7.51）。通常，（-）-异构体比（+）-异构体更有效。结合结果表明对化合物（-）-10中的D3受体具有最高选择性（K i = 0.35 nM； D2 / D3 = 71）。在5-羟基系列中，化合物（-）-25（K i = 0.）对D3受体的选择性最高。82 nM；D2 / D3 = 31.5）。大多数有效的化合物在亚纳摩尔水平上对D3受体表现出结合和功能亲和力。用tri化的烯酮作为放​​射性配体，用表达D2或D3受体的HEK-
• Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors
  作者：Bhaskar Gopishetty、Suhong Zhang、Prashant S. Kharkar、Tamara Antonio、Maarten Reith、Aloke K. Dutta

  DOI：10.1016/j.bmc.2013.03.059

  日期：2013.6

  The goal of the present study was to explore, in our previously developed hybrid template, the effect of introduction of additional heterocyclic rings (mimicking catechol hydroxyl groups as bioisosteric replacement) on selectivity and affinity for the D-3 versus D-2 receptor. In addition, we wanted to explore the effect of derivatization of functional groups of the agonist binding moiety in compounds developed by us earlier from the hybrid template. Binding affinity (K-i) of the new compounds was measured with tritiated spiperone as the radioligand and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed in the GTP gamma S binding assay. In the imidazole series, compound 10a exhibited the highest D-3 affinity whereas the indole derivative 13 exhibited similar high D-3 affinity. Functionalization of the amino group in agonist (+)-9d with different sulfonamides derivatives improved the D-3 affinity significantly with (+)-14f exhibiting the highest affinity. However, functionalization of the hydroxyl and amino groups of 15 and (+)-9d, known agonist and partial agonist, to sulfonate ester and amide in general modulated the affinity. In both cases loss of agonist potency resulted from such derivatization. (C) 2013 Elsevier Ltd. All rights reserved.