N-{4-[4-(4-Benzyl-piperidin-1-yl)-but-1-ynyl]-phenyl}-acetamide

• 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: N-{4-[4-(4-Benzyl-piperidin-1-yl)-but-1-ynyl]-phenyl}-acetamide
• 英文别名: N-[4-[4-(4-benzylpiperidin-1-yl)but-1-ynyl]phenyl]acetamide
• 化学式: C₂₄H₂₈N₂O
• 分子量: 360.499
• InChiKey: XRVOIGOCEXMZCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-苄基哌啶 在 四氢吡咯 、 四(三苯基膦)钯 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 N-{4-[4-(4-Benzyl-piperidin-1-yl)-but-1-ynyl]-phenyl}-acetamide
  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

文献信息

• 4-Substituted piperidine analogs and their use as subtype selective NMDA receptor, antagonists
  申请人：——

  公开号：US20030105133A1

  公开（公告）日：2003-06-05

  Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, glaucoma, CMV retinitis, chronic pain, opioid tolerance or withdrawals, or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Also described are novel methods for preparing 4-substituted piperidine analogs and novel intermediates of the 4-substituted piperidine analogs.

  本文介绍了新型4-取代哌啶类似物、含有相同成分的制药组合物以及使用4-取代哌啶类似物作为选择性活性N-甲基-D-天门冬氨酸（NMDA）受体亚型拮抗剂治疗中风、脑缺血、中枢神经系统创伤、低血糖、焦虑、惊厥、氨基糖苷类抗生素引起的听力损失、偏头痛、青光眼、巨细胞病毒性视网膜炎、慢性疼痛、阿片类耐受或戒断综合征或神经退行性疾病，如拉蒂病、阿尔茨海默病、帕金森病和亨廷顿病的条件。还介绍了制备4-取代哌啶类似物的新方法和4-取代哌啶类似物的新中间体。
• 4-SUBSTITUTED PIPERIDINE ANALOGS AND THEIR USE AS SUBTYPE SELECTIVE NMDA RECEPTOR ANTAGONISTS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0869791A1

  公开（公告）日：1998-10-14
• EP0869791A4
  申请人：——

  公开号：EP0869791A4

  公开（公告）日：1999-04-28
• US6130234A
  申请人：——

  公开号：US6130234A

  公开（公告）日：2000-10-10
• US6448270B1
  申请人：——

  公开号：US6448270B1

  公开（公告）日：2002-09-10