1-苄基-4-[(4-氟苯基)甲基]哌啶-4-醇 | 193357-11-8

• 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-氟苯基)甲基]哌啶-4-醇
• 英文名称: 1-benzyl-4-(4-fluorobenzyl)-4-hydroxypiperidine
• 英文别名: 1-Benzyl-4-(4-fluoro-benzyl)-piperidin-4-ol；1-benzyl-4-[(4-fluorophenyl)methyl]piperidin-4-ol
• CAS: 193357-11-8
• 化学式: C₁₉H₂₂FNO
• 分子量: 299.388
• InChiKey: SPXWVGAGMKJNME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 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：

  1-苄基-4-[(4-氟苯基)甲基]哌啶-4-醇 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 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
• 作为产物：
  描述：

  N-苄基哌啶酮 、 4-氟氯苄 在 magnesium 、 1,2-二溴乙烷 作用下， 生成 1-苄基-4-[(4-氟苯基)甲基]哌啶-4-醇
  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

• Derivatives of 3-phenyl-n-(2-(4-benzyl)-piperidin-1-yl)-ethyl)-acrylamid with ccr-3-receptor antagonistic activity for use in the treatment of inflammations and allergic conditions
  申请人：——

  公开号：US20040180926A1

  公开（公告）日：2004-09-16

  This invention relates to organic compounds of formula I, 1 in which Ar 1 is unsubstituted phenyl substituted by one or more halogen atoms; Ar 2 is unsubstituted phenyl or phenyl substituted by one or more substituents selected from the group consisting of halogen, cyano and C 1 -C 8 -alkoxy; R 1 is hydrogen or methyl optionally substituted by hydroxy; R 10 is hydrogen or hydroxy; and pharmaceutically acceptable salts thereof. Compositions containing them, methods for their preparation and their use as pharmaceuticals are also described.

  该发明涉及公式I的有机化合物，其中Ar1是未取代的苯基，被一个或多个卤素原子取代；Ar2是未取代的苯基或被一个或多个取代基所取代的苯基，所述取代基选择自卤素、氰基和C1-C8-烷氧基的群体；R1是氢或甲基，可选地被羟基取代；R10是氢或羟基；以及其药学上可接受的盐。还描述了含有它们的组合物、它们的制备方法以及作为药物的用途。
• US06124323
  申请人：——

  公开号：——

  公开（公告）日：——
• EP0869792A4
  申请人：——

  公开号：EP0869792A4

  公开（公告）日：1999-09-22
• 4-SUBSTITUTED PIPERIDINE ANALOGS AND THEIR USE AS SUBTYPE SELECTIVE NMDA RECEPTOR ANTAGONISTS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0869792A2

  公开（公告）日：1998-10-14
• DERIVATIVES OF 3-PHENYL-N-(2- (4-BENZYL) PIPERIDIN-1-YL)-ETHYL)-ACRYLAMID WITH CCR-3 RECEPTOR ANTAGONISTIC ACTIVITY FOR USE IN THE TREATMENT OF INFLAMMATIONS AND ALLERGIC CONDITIONS
  申请人：Novartis AG

  公开号：EP1401814A1

  公开（公告）日：2004-03-31