1'-benzylspiro[6,7,8,9-tetrahydro-5H-benzocyclohepten-5,4'-piperidine] | 137730-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1'-benzylspiro[6,7,8,9-tetrahydro-5H-benzocyclohepten-5,4'-piperidine]
• 英文别名: 1'-benzyl-6,7,8,9-tetrahydrospiro(5H-benzocycloheptene-5,4'-piperidine)；1'-benzylspiro[6,7,8,9-tetrahydrobenzo[7]annulene-5,4'-piperidine]
• CAS: 137730-62-2
• 化学式: C₂₂H₂₇N
• 分子量: 305.463
• InChiKey: XZCHMODGNZASPX-UHFFFAOYSA-N

物化性质

• 沸点：
  433.0±34.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1'-benzylspiro[6,7,8,9-tetrahydro-5H-benzocyclohepten-5,4'-piperidine] 在 palladium dihydroxide 甲酸 、 氢气 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 spiro[6,7,8,9-tetrahydro-5H-benzocyclohepten-5,4'-piperidine]
  参考文献：
  名称：

  Spiropiperidines as high-affinity, selective .sigma. ligands.

  摘要：

  A variety of achiral conformationally restricted spirocyclic piperidines have been prepared in an attempt to investigate the functional role of the central sigma-recognition site. All the compounds possessed a lipophilic N-substituent incorporating either a tetralin, indan, or benzocycloheptane skeleton. Their in vitro affinity at the sigma-site was assessed in radioligand displacement experiments with guinea pig cerebellum homogenates using the sigma-specific radioligand [H-3]-N,N'-di-o-tolyguanidine ([H-3]-DTG, [H-3]-6). A study of the structure-activity relationships identified the N-butyl and N-dimethylallyl substituents as the optimum groups for high affinity and selectivity at the sigma-site (e.g., 3,4-dihydro-1'-(3-methylbut-2-enyl)spiro[1H-indene-1,4'-piperidine] (48), pIC50 = 8.9 vs [3H]-6 and greater than 10000-fold selective over the dopamine D2 receptor). Such compounds are amongst the highest affinity sigma-ligands reported to date, with excellent selectivity over the dopamine D2 receptor, and may serve as at useful tool for exploring the physiological role of the sigma-site.

  DOI：

  10.1021/jm00089a013
• 作为产物：
  描述：

  N,N-双(2-氯乙基)苯甲胺 在 氢氧化钾 、 potassium tert-butylate 、 一水合肼 作用下， 以 二甲基亚砜 、 叔丁醇 、 二乙二醇 为溶剂， 反应 7.0h， 生成 1'-benzylspiro[6,7,8,9-tetrahydro-5H-benzocyclohepten-5,4'-piperidine]
  参考文献：
  名称：

  Spiropiperidines as high-affinity, selective .sigma. ligands.

  摘要：

  A variety of achiral conformationally restricted spirocyclic piperidines have been prepared in an attempt to investigate the functional role of the central sigma-recognition site. All the compounds possessed a lipophilic N-substituent incorporating either a tetralin, indan, or benzocycloheptane skeleton. Their in vitro affinity at the sigma-site was assessed in radioligand displacement experiments with guinea pig cerebellum homogenates using the sigma-specific radioligand [H-3]-N,N'-di-o-tolyguanidine ([H-3]-DTG, [H-3]-6). A study of the structure-activity relationships identified the N-butyl and N-dimethylallyl substituents as the optimum groups for high affinity and selectivity at the sigma-site (e.g., 3,4-dihydro-1'-(3-methylbut-2-enyl)spiro[1H-indene-1,4'-piperidine] (48), pIC50 = 8.9 vs [3H]-6 and greater than 10000-fold selective over the dopamine D2 receptor). Such compounds are amongst the highest affinity sigma-ligands reported to date, with excellent selectivity over the dopamine D2 receptor, and may serve as at useful tool for exploring the physiological role of the sigma-site.

  DOI：

  10.1021/jm00089a013

文献信息

• Spirocyclic antipsychotic agents
  申请人：Merck Sharpe & Dohme Ltd.

  公开号：US05324733A1

  公开（公告）日：1994-06-28

  A class of spirocyclic piperidine derivatives are selective ligands at sigma recognition sites and are therefore useful in the treatment and/or prevention of psychiatric disorders. The claimed compounds are of the formula ##STR1## wherein, A and B are hydrogen, Q is a bond, R.sup.11, R.sup.12, and R.sup.13 are as defined in the specification.

  一类螺环型哌啶衍生物是sigma识别位点的选择性配体，因此在治疗和/或预防精神障碍方面非常有用。所述化合物的化学式为##STR1##其中，A和B为氢，Q为键，R.sup.11，R.sup.12和R.sup.13如规范中所定义。
• US5219860A
  申请人：——

  公开号：US5219860A

  公开（公告）日：1993-06-15
• US5324733A
  申请人：——

  公开号：US5324733A

  公开（公告）日：1994-06-28
• Spiropiperidines as high-affinity, selective .sigma. ligands.
  作者：Mark S. Chambers、Raymond Baker、David C. Billington、Anthony K. Knight、D. N. Middlemiss、Eric H. F. Wong

  DOI：10.1021/jm00089a013

  日期：1992.5

  A variety of achiral conformationally restricted spirocyclic piperidines have been prepared in an attempt to investigate the functional role of the central sigma-recognition site. All the compounds possessed a lipophilic N-substituent incorporating either a tetralin, indan, or benzocycloheptane skeleton. Their in vitro affinity at the sigma-site was assessed in radioligand displacement experiments with guinea pig cerebellum homogenates using the sigma-specific radioligand [H-3]-N,N'-di-o-tolyguanidine ([H-3]-DTG, [H-3]-6). A study of the structure-activity relationships identified the N-butyl and N-dimethylallyl substituents as the optimum groups for high affinity and selectivity at the sigma-site (e.g., 3,4-dihydro-1'-(3-methylbut-2-enyl)spiro[1H-indene-1,4'-piperidine] (48), pIC50 = 8.9 vs [3H]-6 and greater than 10000-fold selective over the dopamine D2 receptor). Such compounds are amongst the highest affinity sigma-ligands reported to date, with excellent selectivity over the dopamine D2 receptor, and may serve as at useful tool for exploring the physiological role of the sigma-site.