8-{2-[4-(2,4,5-Trifluorophenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione

• 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-{2-[4-(2,4,5-Trifluorophenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione
• 英文别名: 8-{2-[4-(2,4,5-Trifluoro-phenyl)-piperazin-1-yl]-ethyl}-8-aza-spiro[4.5]decane-7,9-dione；8-[2-[4-(2,4,5-trifluorophenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione
• 化学式: C₂₁H₂₆F₃N₃O₂
• 分子量: 409.452
• InChiKey: AUQZROKGNYIFMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,3-四亚甲基戊二酸酐 在 吡啶 作用下， 反应 7.0h， 生成 8-{2-[4-(2,4,5-Trifluorophenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Fluoro Analogues of 8-{2-[4-(4-Methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as Selective α_1d-Adrenergic Receptor Antagonists

  摘要：

  We have discovered high-affinity antagonists (exemplified by 11 and 12) that are the most selective for alpha(1d)-adrenergic receptors (alpha(1d)-AR) reported to date. In cloned receptor assay systems, 12 displays at least 95-fold selectivity for the alpha(1d)-AR over all other G-protein-coupled receptors tested, and the subtype selectivity of 11 was confirmed in pharmacologically defined isolated tissue preparations.

  DOI：

  10.1021/jm0491391

文献信息

• Compounds specific for the human alpha1d adrenergic receptor and uses thereof
  申请人：——

  公开号：US20020028760A1

  公开（公告）日：2002-03-07

  This invention is directed towards a method of inhibiting activation of a human &agr; 1d adrenergic receptor which comprises contacting the receptor with a compound so as to inhibit activation of the receptor, wherein the compound binds selectively to a human ald adrenergic receptor. This invention provides for a compound which binds selectively to a human &agr; 1d adrenergic receptor. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier. This invention further provides for a method of treating a subject afflicted with a disease which is susceptible to treatment by antagonism of the human &agr; 1d adrenergic receptor which comprises administering to the subject an amount of the above defined compounds effective to treat the disease.

  这项发明涉及一种抑制人类α1d肾上腺素受体激活的方法，包括将受体与一种化合物接触，以抑制受体的激活，其中该化合物选择性地结合到人类α1d肾上腺素受体。这项发明提供了一种选择性结合到人类α1d肾上腺素受体的化合物。该发明还提供了一种包含上述定义的化合物的治疗有效量和药学上可接受的载体的药物组合物。这项发明还提供了一种治疗患有易受人类α1d肾上腺素受体拮抗治疗的疾病的方法，包括向受试者施用上述定义的化合物的有效量以治疗疾病。
• Compounds specific for the human &agr;1d adrenergic receptor and uses thereof
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US06706716B2

  公开（公告）日：2004-03-16

  This invention is directed towards a method of inhibiting activation of a human &agr;1d adrenergic receptor which comprises contacting the receptor with a compound so as to inhibit activation of the receptor, wherein the compound binds selectively to a human &agr;1d adrenergic receptor. This invention provides for a compound which binds selectively to a human &agr;1d adrenergic receptor. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier. This invention further provides for a method of treating a subject afflicted with a disease which is susceptible to treatment by antagonism of the human &agr;1d adrenergic receptor which comprises administering to the subject an amount of the above defined compounds effective to treat the disease.

  本发明涉及一种抑制人类α1d肾上腺素能受体激活的方法，该方法包括将化合物与受体接触以抑制其激活，其中该化合物选择性地结合于人类α1d肾上腺素能受体。本发明提供了一种选择性结合于人类α1d肾上腺素能受体的化合物。本发明还提供了一种制药组合物，包括上述定义的化合物的治疗有效量和药学可接受载体。本发明还提供了一种治疗易受人类α1d肾上腺素能受体拮抗剂治疗的疾病的方法，该方法包括向患者施用上述定义的化合物的有效治疗量以治疗该疾病。
• US6706716B2
  申请人：——

  公开号：US6706716B2

  公开（公告）日：2004-03-16
• Synthesis and Structure−Activity Relationship of Fluoro Analogues of 8-{2-[4-(4-Methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as Selective α_1d-Adrenergic Receptor Antagonists
  作者：Michael J. Konkel、John M. Wetzel、Marie Cahir、Douglas A. Craig、Stewart A. Noble、Charles Gluchowski

  DOI：10.1021/jm0491391

  日期：2005.4.1

  We have discovered high-affinity antagonists (exemplified by 11 and 12) that are the most selective for alpha(1d)-adrenergic receptors (alpha(1d)-AR) reported to date. In cloned receptor assay systems, 12 displays at least 95-fold selectivity for the alpha(1d)-AR over all other G-protein-coupled receptors tested, and the subtype selectivity of 11 was confirmed in pharmacologically defined isolated tissue preparations.