L 690404 | 134697-69-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: L 690404
• 英文别名: 1''-butyl-3,4-dihydro-2H-spiro[naphthalene-1,4''-piperidine]; HCl；1'-butylspiro[2,3-dihydro-1H-naphthalene-4,4'-piperidine]
• CAS: 134697-69-1
• 化学式: C₁₈H₂₇N
• 分子量: 257.419
• InChiKey: GWZNBTHONPZRPP-UHFFFAOYSA-N

物化性质

• 沸点：
  365.7±31.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  β-四氢萘酮 在 palladium dihydroxide 氢氧化钾 、 甲酸 、 potassium tert-butylate 、 氢气 、 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 叔丁醇 、 二乙二醇 为溶剂， 100.0 ℃ 、344.73 kPa 条件下， 反应 26.0h， 生成 L 690404
  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 SHARP & DOHME LTD.

  公开号：EP0414289B1

  公开（公告）日：1994-02-23
• 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.