1-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-piperidine-3-carboxylic acid | 143790-25-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-piperidine-3-carboxylic acid
• 英文别名: 1-[4-(4-Fluorophenyl)-4-oxobutyl]piperidine-3-carboxylic acid
• CAS: 143790-25-4
• 化学式: C₁₆H₂₀FNO₃
• 分子量: 293.338
• InChiKey: UTINUIORGRIRTF-UHFFFAOYSA-N

物化性质

• 沸点：
  471.2±45.0 °C(predicted)
• 密度：
  1.202±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-哌啶甲酸乙酯 在 lithium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 79.0h， 生成 1-[4-(4-Fluoro-phenyl)-4-oxo-butyl]-piperidine-3-carboxylic acid
  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

文献信息

• Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake
  作者：Michael R. Pavia、Sandra J. Lobbestael、David Nugiel、Daniel R. Mayhugh、Vlad E. Gregor、Charles P. Taylor、Roy D. Schwarz、Laura Brahce、Mark G. Vartanian

  DOI：10.1021/jm00100a032

  日期：1992.10

  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.