1-<2-(4-benzyloxyphenyl)ethoxy>-4-(4-fluorobenzyl)piperidine | 193357-64-1

• 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: 1-<2-(4-benzyloxyphenyl)ethoxy>-4-(4-fluorobenzyl)piperidine
• 英文别名: 1-[2-(4-benzyloxyphenoxy)ethyl]-4-(4-fluorobenzyl)piperidine；4-[(4-Fluorophenyl)methyl]-1-[2-(4-phenylmethoxyphenoxy)ethyl]piperidine
• CAS: 193357-64-1
• 化学式: C₂₇H₃₀FNO₂
• 分子量: 419.539
• InChiKey: LJYKYWDCBVNSJX-UHFFFAOYSA-N

物化性质

• 沸点：
  555.5±40.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<2-(4-benzyloxyphenyl)ethoxy>-4-(4-fluorobenzyl)piperidine 在 palladium-carbon 作用下， 以 甲醇 为溶剂， 以3.2 g (95%)的产率得到4-(4-fluorobenzyl)-1-<2-(4-hydroxyphenyl)ethoxy>piperidine hydrochloride
  参考文献：
  名称：

  US6124323

  摘要：

  公开号：
• 作为产物：
  描述：

  4-苄氧基苯酚 在 potassium carbonate 作用下， 以 正己烷 、 乙酸乙酯 、 乙腈 为溶剂， 生成 1-<2-(4-benzyloxyphenyl)ethoxy>-4-(4-fluorobenzyl)piperidine
  参考文献：
  名称：

  US6124323

  摘要：

  公开号：

文献信息

• 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.
• 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
• US6124323A
  申请人：——

  公开号：US6124323A

  公开（公告）日：2000-09-26
• [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 RECEPTEUR DE NMDA
  申请人：——

  公开号：WO1997023216A1

  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 are selective active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, psychosis, anxiety, migraine headaches, glaucoma, CMV retinitis, aminoglycoside antibiotics-induced hearing loss, convulsions, chronic pain, opioid tolerance or withdrawal, urinary incontinence or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described.
  [FR] Cette invention concerne de nouveaux analogues de pipéridine à substitution en position 4, des compositions pharmaceutiques contenant ces derniers ainsi que le procédé d'utilisation d'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, la psychose, l'anxiété, les maux de tête migraineux, le glaucome, la rétinite à cytomégalovirus, la perte des cheveux induite par les antibiotiques à base d'aminosides, les convulsions, la douleur chronique, la tolérance aux opioïdes ou l'arrêt des opioïdes, l'incontinence urinaire ou les maladies neurodégénératives telles que le lathyrisme, la maladie d'Alzheimer, la maladie de Parkinson et la maladie de Huntington.