1-<2-(4-benzyloxyphenyl)ethoxy>-4-hydroxy-4-(4-methylbenzyl)piperidine hydrochloride | 193357-90-3

• 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-hydroxy-4-(4-methylbenzyl)piperidine hydrochloride
• 英文别名: 1-[2-(4-Benzyloxyphenoxy)ethyl]-4-hydroxy4-(4-methylbenzyl) piperidine hydrochloride；1-[2-(4-benzyloxyphenoxy)ethyl]-4-hydroxy-4-(4-methylbenzyl)piperidine hydrochloride；4-[(4-methylphenyl)methyl]-1-[2-(4-phenylmethoxyphenoxy)ethyl]piperidin-4-ol;hydrochloride
• CAS: 193357-90-3
• 化学式: C₂₈H₃₃NO₃*ClH
• 分子量: 468.036
• InChiKey: XIOPPSQDBDQUKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.61
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  43.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<2-(4-benzyloxyphenyl)ethoxy>-4-hydroxy-4-(4-methylbenzyl)piperidine hydrochloride 在 palladium dihydroxide 氢气 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以100%的产率得到1-[2-(4-hydroxyphenoxy)ethyl]-4-hydroxy-4-(4-methylbenzyl)-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
• 作为产物：
  描述：

  4-甲基氯苄 在 palladium-carbon 盐酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 生成 1-<2-(4-benzyloxyphenyl)ethoxy>-4-hydroxy-4-(4-methylbenzyl)piperidine hydrochloride
  参考文献：
  名称：

  US6124323

  摘要：

  公开号：

文献信息

• Method for treating diseased-related or drug-induced dyskinesias
  申请人：——

  公开号：US06284776B1

  公开（公告）日：2001-09-04

  Dyskinesias in humans are treated by administering a therapeutically effective dose of an NR1A/2B site-selective NMDA receptor antagonist compound to a human suffering therefrom.

  人类的运动障碍症状可以通过给患者口服一种NR1A/2B位点选择性NMDA受体拮抗剂的治疗剂量来治疗。
• 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
• METHOD FOR TREATING DISEASE-RELATED OR DRUG-INDUCED DYSKINESIAS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1024799A1

  公开（公告）日：2000-08-09