1-{2-[Bis-(3,4-dichloro-phenyl)-methoxy]-ethyl}-piperidine-3-carboxylic acid ethyl ester | 128173-78-4

• 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-{2-[Bis-(3,4-dichloro-phenyl)-methoxy]-ethyl}-piperidine-3-carboxylic acid ethyl ester
• CAS: 128173-78-4
• 化学式: C₂₃H₂₅Cl₄NO₃
• 分子量: 505.268
• InChiKey: RUFHHOOYDYHRBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.68
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  38.77
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-{2-[Bis-(3,4-dichloro-phenyl)-methoxy]-ethyl}-piperidine-3-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 64.0h， 生成 3-piperidinecarboxylic acid, 1-[2-[bis(3,4-dichlorophenyl)methoxy]ethyl]-
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032
• 作为产物：
  描述：

  3,4-二氯溴苯 在 硫酸 、 potassium carbonate 、 magnesium 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 21.0h， 生成 1-{2-[Bis-(3,4-dichloro-phenyl)-methoxy]-ethyl}-piperidine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032