CSP 2503 | 581813-10-7

• 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: CSP 2503
• 英文别名: Pyrrolo(1,2-a)pyrazine-1,4-dione, hexahydro-2-((4-(1-naphthalenyl)-1-piperazinyl)methyl)-, (8aS)-；(8aS)-2-[(4-naphthalen-1-ylpiperazin-1-yl)methyl]-6,7,8,8a-tetrahydro-3H-pyrrolo[1,2-a]pyrazine-1,4-dione
• CAS: 581813-10-7
• 化学式: C₂₂H₂₆N₄O₂
• 分子量: 378.474
• InChiKey: CTZWGZSINBFHFD-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  47.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 1-(1-萘基)对二氮已环 、 (8As)-六氢吡咯并[1,2-a]吡嗪-1,4-二酮 以 乙醇 为溶剂， 生成 CSP 2503
  参考文献：
  名称：

  S-（-）-2-[[4-（萘-1-基）哌嗪-1-基]甲基] -1,4-二氧杂氢吡咯并[1,2-a]吡嗪的设计与合成（CSP-2503）使用计算仿真。5-HT1A受体激动剂。

  摘要：

  基于5-HT（1A）R-配体相互作用的计算模型和QSAR研究，我们设计和合成了一系列新的芳基哌嗪2-8，它们在α（1）上具有较高的5-HT（1A）R亲和力和选择性肾上腺素能受体。其中，化合物CSP-2503（4）的药理学特征是在体树突状和突触后部位具有抗焦虑特性的5-HT（1A）R激动剂。

  DOI：

  10.1016/s0960-894x(03)00160-4

文献信息

• Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 8. Computational Simulation of Ligand−Receptor Interaction of 5-HT_1AR Agonists with Selectivity over α₁-Adrenoceptors
  作者：María L. López-Rodríguez、Maria José Morcillo、Esther Fernández、Bellinda Benhamú、Ignacio Tejada、David Ayala、Alma Viso、Mercedes Campillo、Leonardo Pardo、Mercedes Delgado、Jorge Manzanares、José A. Fuentes

  DOI：10.1021/jm048999e

  日期：2005.4.1

  We have designed and synthesized a new series of arylpiperazines V exhibiting high 5-HT1AR affinity and selectivity over alpha(1)-adrenoceptors. The new selective 5-HT1AR ligands contain a hydantoin (m = 0) or diketopiperazine (m = 1) moiety and an arylpiperazine moiety separated by one methylene unit (n = 1). The aryl substituent of the piperazine moiety (Ar) consists of different benzofused rings mimicking the favorable voluminous substituents at ortho and meta positions predicted by 3D-QSAR analysis in the previously reported series I. In particular, (S)-2-[[4-(naphth-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-a]pyrazine [(S)-9, CSP-2503] (5-HT1A, K-i = 4.1 nM; alpha(1), Ki > 1000 nM) has been pharmacologically characterized as a 5-HT1AR agonist at somatodendritic and postsynaptic sites, endowed with anxiolytic properties. Ligand (S)-9 is predicted, in computer simulations, to bind Asp(3.32) in TMH 3, Thr(5.39) and Ser(5.42) in TMH 5, and Trp(6.48) in TMH 6. We propose that agonists modify, by means of an explicit hydrogen bond, the conformation of Trp(6.48) from pointing toward TMH 7, in the inactive gauche+ conformation, to pointing toward the ligand binding site, in the active trans conformation.