7-(4-(3,4-dihydroisoquinolin-2-yl)butyl)-8-ethoxy-1,3-dimethylpurine-2,6-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 7-(4-(3,4-dihydroisoquinolin-2-yl)butyl)-8-ethoxy-1,3-dimethylpurine-2,6-dione
• 英文别名: 7-[4-(1,2,3,4-Tetrahydroisoquinolin-2-yl)-butyl]-8-ethoxy-1,3-dimethyl-3,7-dihydropurine-2,6-dione；7-[4-(3,4-dihydro-1H-isoquinolin-2-yl)butyl]-8-ethoxy-1,3-dimethylpurine-2,6-dione
• 化学式: C₂₂H₂₉N₅O₃
• 分子量: 411.504
• InChiKey: XBFHDMFDVXKYEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 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：
  70.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-溴茶碱 在 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 丙醇 、 乙醇 、 丙酮 为溶剂， 反应 70.0h， 生成 7-(4-(3,4-dihydroisoquinolin-2-yl)butyl)-8-ethoxy-1,3-dimethylpurine-2,6-dione
  参考文献：
  名称：

  8-烷氧基嘌呤-2,6-二酮的氨基烷基衍生物：多功能 5-HT1A/5-HT7 受体配体和具有抗抑郁活性的 PDE 抑制剂

  摘要：

  在寻找潜在的精神药物时，一系列新的芳基哌嗪、全氢异喹啉或四氢异喹啉的 3,7-二甲基-和 1,3-二甲基-8-烷氧基嘌呤-2,6-二酮衍生物与柔性亚烷基间隔（5-16和 21-32) 被合成并评估了 5-HT1A/5-HT7 受体亲和力以及 PDE4B1 和 PDE10A 抑制特性。1-(4-(4-(2-羟基苯基)哌嗪-1-基)丁基)-3,7-二甲基-8-丙氧基嘌呤-2,6-二酮(16)和7-(2-羟基苯基)哌嗪基烷基‐1,3-二甲基-8-乙氧基嘌呤-2,6-二酮（31 和 32）作为有效的双 5-HT1A/5-HT7 受体配体，具有拮抗活性，在小鼠强迫游泳试验中产生抗抑郁样作用。这种效果类似于西酞普兰产生的效果。所有测试的化合物都是比茶碱和可可碱更强的磷酸二酯酶同工酶抑制剂。最有效的化合物 15 和 16 的特征在于，在 10-5 M 的浓度下，PDE4B1 活性的抑制率分别为 51% 和

  DOI：

  10.1002/ardp.201600260

文献信息

• 7-Arylpiperazinylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and some of their purine-2,6,8-trione analogs as 5-HT1A, 5-HT2A, and 5-HT7 serotonin receptor ligands
  作者：Grażyna Chłoń-Rzepa、Paweł Żmudzki、Paweł Zajdel、Andrzej J. Bojarski、Beata Duszyńska、Agnieszka Nikiforuk、Ewa Tatarczyńska、Maciej Pawłowski

  DOI：10.1016/j.bmc.2007.05.017

  日期：2007.8

  On the basis of our earlier studies with the serotonin receptor ligands in the group of 1,3-dimetliyl-3,7-dihydropurine-2, 6-dione derivatives. a series of new arylpiperazinylalkyl and tetrahydroisocluinolinylalkyl analogs of 8-alkoxy-1,3-dimethyl-3,7-dihydropurine-2,6-dione (10-25) and 1,3-dimethyl-7,9-dihydro-3H-purine-2,6,8-trione (26-30) were synthesized and their 5-HT1A, 5-HT2A, and 5-HT7 receptor affinities were determined. The new compounds 17, 18, 20, and 21 were found to be highly active 5-HT1A receptor ligands (K-i = 11-19 nM) with diversified affinity for 5-HT2A receptors (K-i = 15-253 nM). Compounds 12, 13, 15, and 19 were moderately potent 5-HT2A ligands (K-i = 23-57 nM), whereas 17, 18, 24, and 25 showed distinct affinity for 5-HT7 receptors (Ki = 51-83 nM). Purine-2,6,8-triones showed weak affinities for 5-HT2A and 5-HT7 receptors; among them, 27 and 29 were classified as 5-HT2A receptor ligands.The selected compounds 17 and 21 were pharmacologically evaluated to determine their functional activities at pre-(hypothermia in mice) and post-(lower lip retraction in rats) synaptic 5-HT1A receptors. Compound 17 showed features of a potential agonist of pre- and post-synaptic 5-HT1A receptors, whereas 21 was classified as a potential, weak partial agonist of postsynaptic sites. Last of all, the most interesting compound 17 tested in behavioral models showed potential anxiolytic and antidepressant activities. (c) 2007 Elsevier Ltd. All rights reserved.