4-(4-fluorobenzyl)-1-but-3-ynyl-4-hydroxypiperidine | 231947-14-1

• 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: 4-(4-fluorobenzyl)-1-but-3-ynyl-4-hydroxypiperidine
• 英文别名: 1-But-3-ynyl-4-[(4-fluorophenyl)methyl]piperidin-4-ol
• CAS: 231947-14-1
• 化学式: C₁₆H₂₀FNO
• 分子量: 261.339
• InChiKey: SRIJCZBBQJJYMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-fluorobenzyl)-1-but-3-ynyl-4-hydroxypiperidine 、 alkaline earth salt of/the/ methylsulfuric acid 在 四氢吡咯 、 四(三苯基膦)钯 作用下， 反应 72.0h， 生成 1-[4-(4-Amino-phenyl)-but-3-ynyl]-4-(4-fluoro-benzyl)-piperidin-4-ol
  参考文献：
  名称：

  Subtype-Selective N-Methyl-d-aspartate Receptor Antagonists:  Synthesis and Biological Evaluation of 1-(Arylalkynyl)-4-benzylpiperidines

  摘要：

  A search of our compound library for compounds with structural similarity to ifenprodil (5) and haloperidol (7) followed by in vitro screening revealed that 4-benzyl-1-(4-phenyl-3-butynyl)-piperidine (8) was a moderately potent and selective antagonist of the NR1A/2B subtype of NMDA receptors. Substitution on the benzyl group of 8 did not significantly affect NR1A/2B potency, while addition of hydrogen bond donors in the para position of the phenyl group enhanced NR1A/2B potency. Addition of a hydroxyl moiety to the 4-position of the piperidine group slightly reduced NR1A/2B potency while reducing alpha-1 adrenergic and dopamine D2 receptor binding affinities substantially, resulting in improved overall selectivity for NR1A/2B receptors. Finally, the butynyl linker was replaced with propynyl or pentynyl. When the phenyl was para substituted with amine or acetamide groups, the NR1A/2B potency order was butynyl > pentynyl >> propynyl. For the para methanesulfonamide or hydroxyl groups, the order was butynyl approximate to propynyl > pentynyl. The hydroxyl propyne (48) and butyne (23) were among the most potent NR1A/2B antagonists from this study. They both potentiated the effects of L-DOPA in the 6-hydroxydopamine-lesioned rat, a model of Parkinson's disease, dosed at 10 mg/kg ip, but 48 was not active at 30 mg/kg po.

  DOI：

  10.1021/jm990148x
• 作为产物：
  描述：

  N-苄基哌啶酮 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 magnesium 、 溶剂黄146 、 1,2-二溴乙烷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 4-(4-fluorobenzyl)-1-but-3-ynyl-4-hydroxypiperidine
  参考文献：
  名称：

  Subtype-Selective N-Methyl-d-aspartate Receptor Antagonists:  Synthesis and Biological Evaluation of 1-(Arylalkynyl)-4-benzylpiperidines

  摘要：

  A search of our compound library for compounds with structural similarity to ifenprodil (5) and haloperidol (7) followed by in vitro screening revealed that 4-benzyl-1-(4-phenyl-3-butynyl)-piperidine (8) was a moderately potent and selective antagonist of the NR1A/2B subtype of NMDA receptors. Substitution on the benzyl group of 8 did not significantly affect NR1A/2B potency, while addition of hydrogen bond donors in the para position of the phenyl group enhanced NR1A/2B potency. Addition of a hydroxyl moiety to the 4-position of the piperidine group slightly reduced NR1A/2B potency while reducing alpha-1 adrenergic and dopamine D2 receptor binding affinities substantially, resulting in improved overall selectivity for NR1A/2B receptors. Finally, the butynyl linker was replaced with propynyl or pentynyl. When the phenyl was para substituted with amine or acetamide groups, the NR1A/2B potency order was butynyl > pentynyl >> propynyl. For the para methanesulfonamide or hydroxyl groups, the order was butynyl approximate to propynyl > pentynyl. The hydroxyl propyne (48) and butyne (23) were among the most potent NR1A/2B antagonists from this study. They both potentiated the effects of L-DOPA in the 6-hydroxydopamine-lesioned rat, a model of Parkinson's disease, dosed at 10 mg/kg ip, but 48 was not active at 30 mg/kg po.

  DOI：

  10.1021/jm990148x