(S)-2-(5-(4-(2-(methylthio)phenyl)piperazin-1-yl)pentanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (S)-2-(5-(4-(2-(methylthio)phenyl)piperazin-1-yl)pentanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
• 英文别名: (3S)-2-[5-[4-(2-methylsulfanylphenyl)piperazin-1-yl]pentanoyl]-3,4-dihydro-1H-isoquinoline-3-carboxamide
• 化学式: C₂₆H₃₄N₄O₂S
• 分子量: 466.648
• InChiKey: BPGGMVGSZXHHJH-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-(S)-1,2,3,4-四氢异喹啉-3-羧酸 在 N-甲基吗啉 、 potassium carbonate 、 三乙胺 、 三氟乙酸 、 potassium iodide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 90.58h， 生成 (S)-2-(5-(4-(2-(methylthio)phenyl)piperazin-1-yl)pentanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Towards novel 5-HT7 versus 5-HT1A receptor ligands among LCAPs with cyclic amino acid amide fragments: Design, synthesis, and antidepressant properties. Part II

  摘要：

  A 26-membered library of novel long-chain arylpiperazines, which contained primary and tertiary amides of cyclic amino acids (proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxamide) in the terminal fragment was synthesized and biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors. Docking studies confirmed advantages of Tic-amide over Pro-amide fragment for interaction with 5-HT7 receptors. Selected compounds 32 and 28, which behaved as 5-HT(7)Rs antagonist and 5-HT1A partial agonist, respectively, produced antidepressant-like effects in the forced swim test in mice after acute treatment in doses of 10 mg/kg (32) and 1.25 mg/kg (28). Compound 32 reduced immobility in a manner similar to the selective 5-HT7 antagonist SB-269970. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.041

文献信息

• Solid-supported synthesis, molecular modeling, and biological activity of long-chain arylpiperazine derivatives with cyclic amino acid amide fragments as 5-HT7 and 5-HT1A receptor ligands
  作者：Vittorio Canale、Paweł Guzik、Rafał Kurczab、Pascal Verdie、Grzegorz Satała、Bartłomiej Kubica、Maciej Pawłowski、Jean Martinez、Gilles Subra、Andrzej J. Bojarski、Paweł Zajdel

  DOI：10.1016/j.ejmech.2014.03.005

  日期：2014.5

  A 47-membered library of novel long-chain arylpiperazines, which contained cyclic amino acid amides in the terminal fragment (pyrrolidine-2-carboxamide and 1,2,3,4-tetrahydroisoquinoline-3-carboxamide), was synthesized on Rink-amide resin and biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors. Surprisingly, members of the designed series containing piperidine-2-carboxamide fragments

  在Rink-amide上合成了一个由47个成员组成的新颖长链芳基哌嗪文库，该文库的末端片段中含有环氨基酸酰胺（吡咯烷-2-羧酰胺和1,2,3,4-四氢异喹啉-3-羧酰胺）树脂和生物学评估对5-HT 7和5-HT 1A受体的结合亲和力。出人意料的是，所设计的含有哌啶-2-甲酰胺片段的系列的成员经历了水解过程，该水解过程是在酸性处理过程中发生，以从固体载体上释放出来，水解成它们各自的胡椒酸类似物。库中的代表性化合物对5-HT 7（K i  = 18–3134 nM）和5-HT 1A（K i = 0.5–6307 nM）位点。分子模型支持了所研究化合物与5-HT 7受体结合的可能相互作用。还进行了研究以支持对酰胺片段，亚烷基间隔基的长度以及芳基哌嗪取代基对受体亲和力和选择性的影响的探索。
• Towards novel 5-HT7 versus 5-HT1A receptor ligands among LCAPs with cyclic amino acid amide fragments: Design, synthesis, and antidepressant properties. Part II
  作者：Vittorio Canale、Rafał Kurczab、Anna Partyka、Grzegorz Satała、Jagna Witek、Magdalena Jastrzębska-Więsek、Maciej Pawłowski、Andrzej J. Bojarski、Anna Wesołowska、Paweł Zajdel

  DOI：10.1016/j.ejmech.2014.12.041

  日期：2015.3

  A 26-membered library of novel long-chain arylpiperazines, which contained primary and tertiary amides of cyclic amino acids (proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxamide) in the terminal fragment was synthesized and biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors. Docking studies confirmed advantages of Tic-amide over Pro-amide fragment for interaction with 5-HT7 receptors. Selected compounds 32 and 28, which behaved as 5-HT(7)Rs antagonist and 5-HT1A partial agonist, respectively, produced antidepressant-like effects in the forced swim test in mice after acute treatment in doses of 10 mg/kg (32) and 1.25 mg/kg (28). Compound 32 reduced immobility in a manner similar to the selective 5-HT7 antagonist SB-269970. (C) 2014 Elsevier Masson SAS. All rights reserved.