1-苄基-4-(4-甲基亚苄基)哌啶 | 242487-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-苄基-4-(4-甲基亚苄基)哌啶
• 英文名称: 1-benzyl-4-(4-methylbenzylidene)piperidine
• 英文别名: 1-benzyl-4-(4-methylbenzyl)piperidine；1-Benzyl-4-[(4-methylphenyl)methylidene]piperidine
• CAS: 242487-87-2
• 化学式: C₂₀H₂₃N
• 分子量: 277.409
• InChiKey: HTSWRJLJRDSFDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-苄基-4-(4-甲基亚苄基)哌啶 在 palladium dihydroxide 盐酸 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、344.74 kPa 条件下， 反应 17.0h， 生成
  参考文献：
  名称：

  NR2B选择性N-甲基-D-天冬氨酸拮抗剂：5-取代的苯并咪唑的合成与评价。

  摘要：

  两类5取代的苯并咪唑被确定为N-甲基-d-天冬氨酸（NMDA）受体NR2B亚型的有效拮抗剂。所选化合物与NMDA受体的NR2A，NR2C和NR2D亚型以及hERG通道活性和α（1）-肾上腺素结合相比显示出非常好的选择性。苯并咪唑37a在大鼠角叉菜胶诱导的机械性痛觉过敏试验中显示出色的活性，并且在狗中显示出良好的药代动力学行为。

  DOI：

  10.1021/jm030483s
• 作为产物：
  描述：

  4-甲基氯苄 在 1,3-二甲基-2-咪唑啉酮 、 sodium hydride 作用下， 反应 15.33h， 生成 1-苄基-4-(4-甲基亚苄基)哌啶
  参考文献：
  名称：

  NR2B选择性N-甲基-D-天冬氨酸拮抗剂：5-取代的苯并咪唑的合成与评价。

  摘要：

  两类5取代的苯并咪唑被确定为N-甲基-d-天冬氨酸（NMDA）受体NR2B亚型的有效拮抗剂。所选化合物与NMDA受体的NR2A，NR2C和NR2D亚型以及hERG通道活性和α（1）-肾上腺素结合相比显示出非常好的选择性。苯并咪唑37a在大鼠角叉菜胶诱导的机械性痛觉过敏试验中显示出色的活性，并且在狗中显示出良好的药代动力学行为。

  DOI：

  10.1021/jm030483s

文献信息

• A Practical Synthesis of 4-(Substituted-benzyl)piperidines and (±)-3-(Substituted-benzyl)pyrrolidines via a Wittig Reaction
  作者：Zhang-Lin Zhou、John F. W. Keana

  DOI：10.1021/jo9824697

  日期：1999.5.1
• 4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine:  A Novel, Potent, and Selective NR1/2B NMDA Receptor Antagonist
  作者：Zhang-Lin Zhou、Sui Xiong Cai、Edward R. Whittemore、Christopher S. Konkoy、Stephen A. Espitia、Minhtam Tran、David M. Rock、Linda L. Coughenour、Jon E. Hawkinson、Peter A. Boxer、Christopher F. Bigge、Lawrence D. Wise、Eckard Weber、Richard M. Woodward、John F. W. Keana

  DOI：10.1021/jm990246i

  日期：1999.7.1

  A structure-based search and screen of our compound library identified N-(2-phenoxyethyl)4-benzylpiperidine (8) as a novel N-methyl-D-aspartate (NMDA) receptor antagonist that has high selectivity for the NR1/2B subunit combination (IC50 = 0.63 mu M). We report on the optimization of this lead compound in terms of potency, side effect liability, and in vivo activity. Potency was assayed by electrical recordings in Xenopus oocytes expressing cloned rat NMDA receptors. Side effect liability was assessed by measuring affinity for alpha(1)-adrenergic receptors and inhibition of neuronal K+ channels. Central bioavailability was gauged indirectly by determining anticonvulsant activity in a mouse maximal electroshock (MES) assay. Making progressive modifications to 8, a hydroxyl substituent on the phenyl ring para to the oxyethyl tether (10a) resulted in a similar to 25-fold increase in NR1A/2B potency (IC50 = 0.025 mu M). p-Methyl substitution on the benzyl ring (10b) produced a similar to 3-fold increase in MES activity (ED50 = 0.7 mg/kg iv). Introduction of a second hydroxyl group into the C-4 position on the piperidine ring (10e) resulted in a substantial decrease in affinity for alpha(1) receptors and reduction in inhibition of Kf channels with only a modest decrease in NR1A/2B and MES potencies. Among the compounds described, 10e (4-hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(methylbenzyl)piperidine, Co 101244/PD 174494) had the optimum pharmacological profile and was selected for further biological evaluation.
• NR2B-Selective <i>N</i>-Methyl-<scp>d</scp>-aspartate Antagonists:  Synthesis and Evaluation of 5-Substituted Benzimidazoles
  作者：John A. McCauley、Cory R. Theberge、Joseph J. Romano、Susan B. Billings、Kenneth D. Anderson、David A. Claremon、Roger M. Freidinger、Rodney A. Bednar、Scott D. Mosser、Stanley L. Gaul、Thomas M. Connolly、Cindra L. Condra、Menghang Xia、Michael E. Cunningham、Bohumil Bednar、Gary L. Stump、Joseph J. Lynch、Alison Macaulay、Keith A. Wafford、Kenneth S. Koblan、Nigel J. Liverton

  DOI：10.1021/jm030483s

  日期：2004.4.1

  Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-d-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and alpha(1)-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical

  两类5取代的苯并咪唑被确定为N-甲基-d-天冬氨酸（NMDA）受体NR2B亚型的有效拮抗剂。所选化合物与NMDA受体的NR2A，NR2C和NR2D亚型以及hERG通道活性和α（1）-肾上腺素结合相比显示出非常好的选择性。苯并咪唑37a在大鼠角叉菜胶诱导的机械性痛觉过敏试验中显示出色的活性，并且在狗中显示出良好的药代动力学行为。