3-piperidinecarboxylic acid, 1-[2-[bis(4-chlorophenyl)methoxy]ethyl]- | 110283-69-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-piperidinecarboxylic acid, 1-[2-[bis(4-chlorophenyl)methoxy]ethyl]-
• 英文别名: 1-[2-[Bis(4-chlorophenyl)methoxy]ethyl]piperidine-3-carboxylic acid
• CAS: 110283-69-7
• 化学式: C₂₁H₂₃Cl₂NO₃
• 分子量: 408.325
• InChiKey: UFHSGXOXBRCZTN-UHFFFAOYSA-N

物化性质

• 沸点：
  536.9±50.0 °C(Predicted)
• 密度：
  1.281±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-piperidinecarboxylic acid, 1-[2-[bis(4-chlorophenyl)methoxy]ethyl]- 在 吡啶 、 氨 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 反应 85.5h， 生成 1-<2-ethyl>-3-piperidinecarbonitrile
  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-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 3-piperidinecarboxylic acid, 1-[2-[bis(4-chlorophenyl)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

文献信息

• Various N-substituted 3-piperidine carboxylic acids or N-substituted 3-pyridine-carboxylic acids and derivatives thereof
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0346927A2

  公开（公告）日：1989-12-20

  Nipecotic acid analogs of general formula I active as GABA uptake inhibitors for use to treat epilepsy.

  通式 I 的尼泊金酸类化合物 作为 GABA 摄取抑制剂具有治疗癫痫的活性。
• N-substituted 3-piperidine-or 3-pyridine-carboxylic acids and derivatives thereof
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0221572B1

  公开（公告）日：1991-09-25
• US4772615A
  申请人：——

  公开号：US4772615A

  公开（公告）日：1988-09-20
• US4910312A
  申请人：——

  公开号：US4910312A

  公开（公告）日：1990-03-20
• US5053521A
  申请人：——

  公开号：US5053521A

  公开（公告）日：1991-10-01