8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}-4-methylquinoline

• 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: 8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}-4-methylquinoline
• 英文别名: 6-methoxy-8-(4-(1-(4-methylquinolin-8-yl)piperidin-4-yl)piperazin-1-yl)quinoline；6-methoxy-8-[4-[1-(4-methylquinolin-8-yl)piperidin-4-yl]piperazin-1-yl]quinoline
• 化学式: C₂₉H₃₃N₅O
• 分子量: 467.614
• InChiKey: AZWXAFUKSVZQEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}-4-methylquinoline 在 盐酸 作用下， 以 甲醇 、 乙醚 、 水 为溶剂， 生成 8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}-4-methylquinoline trihydrochloride
  参考文献：
  名称：

  The Synthesis and Biological Evaluation of Quinolyl-piperazinyl Piperidines as Potent Serotonin 5-HT_1AAntagonists

  摘要：

  As part of an effort to identify 5-HT1A antagonists that did not possess typical arylalkylamine or keto/amido-alkyl aryl piperazine scaffolds, prototype compound 10a was identified from earlier work in a combined 5-HT1A antagonist/SSRI program. This quinolyl-piperazinyl piperidine analogue displayed potent, selective 5-HT1A antagonism but suffered from poor oxidative metabolic stability, resulting in low exposure following oral administration. SA R studies, driven primarily by in vitro liver microsomal stability assessment, identified compound lob, which displayed improved oral bioavailability and lower intrinsic clearance. Further changes to the scaffold (e.g., 10r) resulted in a loss in potency. Compound 10b displayed cognitive enhancing effects in a number of animal models of learning and memory, enhanced the antidepressant-like effects of the SSRI fluoxetine, and reversed the sexual dysfunction induced by chronic fluoxetine treatment.

  DOI：

  10.1021/jm1000908
• 作为产物：
  描述：

  6-甲氧基-8-哌嗪-1-基喹啉 、 1-(4-methylquinolin-8-yl)piperidin-4-one 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成 8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}-4-methylquinoline
  参考文献：
  名称：

  The Synthesis and Biological Evaluation of Quinolyl-piperazinyl Piperidines as Potent Serotonin 5-HT_1AAntagonists

  摘要：

  As part of an effort to identify 5-HT1A antagonists that did not possess typical arylalkylamine or keto/amido-alkyl aryl piperazine scaffolds, prototype compound 10a was identified from earlier work in a combined 5-HT1A antagonist/SSRI program. This quinolyl-piperazinyl piperidine analogue displayed potent, selective 5-HT1A antagonism but suffered from poor oxidative metabolic stability, resulting in low exposure following oral administration. SA R studies, driven primarily by in vitro liver microsomal stability assessment, identified compound lob, which displayed improved oral bioavailability and lower intrinsic clearance. Further changes to the scaffold (e.g., 10r) resulted in a loss in potency. Compound 10b displayed cognitive enhancing effects in a number of animal models of learning and memory, enhanced the antidepressant-like effects of the SSRI fluoxetine, and reversed the sexual dysfunction induced by chronic fluoxetine treatment.

  DOI：

  10.1021/jm1000908

文献信息

• Piperazine-piperidine antagonists and agonists of the 5-HT1A receptor
  申请人：Asselin Magda

  公开号：US20070027160A1

  公开（公告）日：2007-02-01

  The present invention relates to novel piperazine-piperidine compounds. The compounds are useful as 5-HT 1A binding agents, particularly as 5-HT 1A receptor antagonists and agonists. These compounds are useful in treating central nervous system disorders, such as cognition disorders, anxiety disorders, depression and sexual dysfunction.

  本发明涉及新型哌嗪-哌啶化合物。这些化合物可用作5-HT1A结合剂，特别是作为5-HT1A受体拮抗剂和激动剂。这些化合物在治疗中枢神经系统疾病方面很有用，如认知障碍、焦虑症、抑郁症和性功能障碍。
• Processes for synthesizing piperazine-piperidine compounds
  申请人：Liu Weiguo

  公开号：US20080058523A1

  公开（公告）日：2008-03-06

  The present invention relates to processes for synthesizing piperazine-piperidine compounds, and compounds useful as 5-HT 1A binding agents, particularly as 5-HT 1A receptor antagonists and agonists. The processes also allow for safer and environmentally tolerant production of these useful compounds.

  本发明涉及合成哌嗪-哌啶化合物的过程，以及用作5-HT1A结合剂的化合物，特别是5-HT1A受体拮抗剂和激动剂。这些过程还允许更安全、更环保地生产这些有用的化合物。
• PIPERAZINE-PIPERIDINE ANTAGONISTS AND AGONISTS OF THE 5-HT1A RECEPTOR
  申请人：Wyeth

  公开号：EP1888559A2

  公开（公告）日：2008-02-20
• PROCESS FOR SYNTHESIZING PIPERAZINE-PIPERIDINE COMPOUNDS
  申请人：Wyeth

  公开号：EP2035384A2

  公开（公告）日：2009-03-18
• Controlled-release formulation of piperazine-piperidine antagonists and agonists of the 5-HT1A receptor having enhanced intestinal dissolution
  申请人：Ku Mannching Sherry

  公开号：US20080199518A1

  公开（公告）日：2008-08-21

  The present invention relates to controlled-release beads comprising diquinoline-substituted piperazine-piperidine compounds, such as 5-fluoro-8-4-[4-[(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}quinoline, or pharmaceutically acceptable salts thereof; to multiple particulate formulations comprising such beads; to methods of preparing such beads; and to methods of treating 5-HT 1A -related disorders using such beads and/or multiple particulate formulations.