(R)-1-(8-(diphenylamino)-8-oxo-1-octyl)-3-piperidinecarboxylic acid ethyl ester | 249278-42-0

• 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: (R)-1-(8-(diphenylamino)-8-oxo-1-octyl)-3-piperidinecarboxylic acid ethyl ester
• 英文别名: ethyl (3R)-1-[8-oxo-8-(N-phenylanilino)octyl]piperidine-3-carboxylate
• CAS: 249278-42-0
• 化学式: C₂₈H₃₈N₂O₃
• 分子量: 450.621
• InChiKey: QBPQWESQMMTOCV-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	8-Bromo-octanoic acid diphenylamide	1026364-39-5	C20H24BrNO	374.321

反应信息

• 作为反应物：
  描述：

  (R)-1-(8-(diphenylamino)-8-oxo-1-octyl)-3-piperidinecarboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (R)-1-(7-Diphenylcarbamoyl-heptyl)-piperidine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of Novel GABA Uptake Inhibitors. 4. Bioisosteric Transformation and Successive Optimization of Known GABA Uptake Inhibitors Leading to a Series of Potent Anticonvulsant Drug Candidates

  摘要：

  By bioisosteric transformations and successive optimization of known GABA uptake inhibitors, several series of novel GABA uptake inhibitors have been prepared by different synthetic approaches. These compounds are derivatives of nipecotic acid and guvacine, substituted at the nitrogen of these amino acids by various lipophilic moieties such as diarylaminoalkoxyalkyl or diarylalkoxyalkyl. The in vitro values for inhibition of [H-3]GABA uptake in rat synaptosomes was determined for each compound, and it was found that the most potent compound from this series, (R)-1-(2-(3,3-diphenyl-1-propyloxy)ethyl)-3-piperidinecarboxylic acid hydrochloride (29), is so far the most potent parent compound inhibiting GABA uptake into synaptosomes. Structure-activity results confirm our earlier observations, that an electronegative center in the chain connecting the amino acid and diaryl moiety is very critical in order to obtain high in vitro potency. Several of the novel compounds were also evaluated for their ability in vivo to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). Some of the compounds tested show a high in vivo potency comparable with that of the recently launched anticonvulsant product 6 ((R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid).

  DOI：

  10.1021/jm980492e
• 作为产物：
  描述：

  8-溴辛酰氯 在 sodium hydride 、 potassium carbonate 作用下， 以 二丁醚 、 丙酮 为溶剂， 反应 14.0h， 生成 (R)-1-(8-(diphenylamino)-8-oxo-1-octyl)-3-piperidinecarboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis of Novel GABA Uptake Inhibitors. 4. Bioisosteric Transformation and Successive Optimization of Known GABA Uptake Inhibitors Leading to a Series of Potent Anticonvulsant Drug Candidates

  摘要：

  By bioisosteric transformations and successive optimization of known GABA uptake inhibitors, several series of novel GABA uptake inhibitors have been prepared by different synthetic approaches. These compounds are derivatives of nipecotic acid and guvacine, substituted at the nitrogen of these amino acids by various lipophilic moieties such as diarylaminoalkoxyalkyl or diarylalkoxyalkyl. The in vitro values for inhibition of [H-3]GABA uptake in rat synaptosomes was determined for each compound, and it was found that the most potent compound from this series, (R)-1-(2-(3,3-diphenyl-1-propyloxy)ethyl)-3-piperidinecarboxylic acid hydrochloride (29), is so far the most potent parent compound inhibiting GABA uptake into synaptosomes. Structure-activity results confirm our earlier observations, that an electronegative center in the chain connecting the amino acid and diaryl moiety is very critical in order to obtain high in vitro potency. Several of the novel compounds were also evaluated for their ability in vivo to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). Some of the compounds tested show a high in vivo potency comparable with that of the recently launched anticonvulsant product 6 ((R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid).

  DOI：

  10.1021/jm980492e

文献信息

• Synthesis of Novel GABA Uptake Inhibitors. 4. Bioisosteric Transformation and Successive Optimization of Known GABA Uptake Inhibitors Leading to a Series of Potent Anticonvulsant Drug Candidates
  作者：Knud Erik Andersen、Jan L. Sørensen、Per O. Huusfeldt、Lars J. S. Knutsen、Jesper Lau、Behrend F. Lundt、Hans Petersen、Peter D. Suzdak、Michael D. B. Swedberg

  DOI：10.1021/jm980492e

  日期：1999.10.1

  By bioisosteric transformations and successive optimization of known GABA uptake inhibitors, several series of novel GABA uptake inhibitors have been prepared by different synthetic approaches. These compounds are derivatives of nipecotic acid and guvacine, substituted at the nitrogen of these amino acids by various lipophilic moieties such as diarylaminoalkoxyalkyl or diarylalkoxyalkyl. The in vitro values for inhibition of [H-3]GABA uptake in rat synaptosomes was determined for each compound, and it was found that the most potent compound from this series, (R)-1-(2-(3,3-diphenyl-1-propyloxy)ethyl)-3-piperidinecarboxylic acid hydrochloride (29), is so far the most potent parent compound inhibiting GABA uptake into synaptosomes. Structure-activity results confirm our earlier observations, that an electronegative center in the chain connecting the amino acid and diaryl moiety is very critical in order to obtain high in vitro potency. Several of the novel compounds were also evaluated for their ability in vivo to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). Some of the compounds tested show a high in vivo potency comparable with that of the recently launched anticonvulsant product 6 ((R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid).