4-benzyl-1-<2-(4-hydroxyphenyl)ethoxy>piperidine hydrochloride

• 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-benzyl-1-<2-(4-hydroxyphenyl)ethoxy>piperidine hydrochloride
• 英文别名: 1-[2-(4-hydroxyphenoxy)ethyl]-4-benzylpiperidine hydrochloride；4-[2-(4-benzylpiperidin-1-yl)ethoxy]phenol;hydrochloride
• 化学式: C₂₀H₂₅NO₂*ClH
• 分子量: 347.885
• InChiKey: GXJLFWUYNDTSHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.69
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  33.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-苄氧基苯酚 在 palladium on activated charcoal 盐酸 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 50.0h， 生成 4-benzyl-1-<2-(4-hydroxyphenyl)ethoxy>piperidine hydrochloride
  参考文献：
  名称：

  4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine:  A Novel, Potent, and Selective NR1/2B NMDA Receptor Antagonist

  摘要：

  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.

  DOI：

  10.1021/jm990246i

文献信息

• US6124323
  申请人：——

  公开号：——

  公开（公告）日：——
• 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
• US6124323A
  申请人：——

  公开号：US6124323A

  公开（公告）日：2000-09-26