4-(4-methylbenzyl)-1-but-3-ynylpiperidine | 192990-02-6

• 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-methylbenzyl)-1-but-3-ynylpiperidine
• 英文别名: 1-But-3-ynyl-4-[(4-methylphenyl)methyl]piperidine
• CAS: 192990-02-6
• 化学式: C₁₇H₂₃N
• 分子量: 241.376
• InChiKey: VQDSNCTXXPAAMC-UHFFFAOYSA-N

物化性质

• 沸点：
  351.1±25.0 °C(Predicted)
• 密度：
  0.979±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  4-(4-methylbenzyl)-1-but-3-ynylpiperidine 、 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 4-{4-[4-(4-Methyl-benzyl)-piperidin-1-yl]-but-1-ynyl}-phenylamine
  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：

  4-吡啶甲醛 在 palladium on activated charcoal 盐酸 、 正丁基锂 、 氢气 、 碳酸氢钠 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.25h， 生成 4-(4-methylbenzyl)-1-but-3-ynylpiperidine
  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：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
• [EN] 4-SUBSTITUTED PIPERIDINE ANALOGS AND THEIR USE AS SUBTYPE SELECTIVE NMDA RECEPTOR ANTAGONISTS<br/>[FR] ANALOGUES DE PIPERIDINE A SUBSTITUTION EN POSITION 4 ET UTILISATION DE CES DERNIERS EN TANT QU'ANTAGONISTES SELECTIVEMENT ACTIFS CONTRE LES SOUS-TYPES DU RECEPTEURS DE NMDA
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1997023214A1

  公开（公告）日：1997-07-03

  (EN) 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.(FR) Cette invention concerne des analogues de pipéridine à substitution en position 4, des compositions pharmaceutiques contenant ces derniers ainsi que le procédé d'utilisation desdits analogues de pipéridine à substitution en position 4 en tant qu'antagonistes sélectivement actifs contre les sous-types du récepteur de N-méthyl-D-aspartate (NMDA) pour traiter des états pathologiques tels que l'attaque, l'ischémie cérébrale, le traumatisme du système nerveux central, l'hypoglycémie, l'anxiété, les convulsions, la perte d'audition induite par les antibiotiques aminoglucosides, les maux de tête migraineux, le glaucome, la rétinite à cytomégalovirus, la douleur chronique, la tolérance aux opioïdes ou le sevrage des opioïdes ou bien des maladies neurodégénératives telles que le lathyrisme, la maladie d'Alzheimer, la maladie de Parkinson et la maladie de Huntington. Cette invention concerne également de nouveaux procédés de préparation d'analogues de pipéridine à substitution en position 4 et de nouveaux intermédiaires desdits analogues de pipéridine à substitution en position 4.