4-(3,5-dihydroxy-benzyl)-piperazine-1-carboxylic acid tert-butyl ester | 847375-10-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(3,5-dihydroxy-benzyl)-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[(3,5-dihydroxyphenyl)methyl]piperazine-1-carboxylate
• CAS: 847375-10-4
• 化学式: C₁₆H₂₄N₂O₄
• 分子量: 308.378
• InChiKey: OYQUWLIHARZIGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3,5-dihydroxy-benzyl)-piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 WAY-267464
  参考文献：
  名称：

  Flexible analogues of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin 1 a receptors

  摘要：

  A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V-1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY -267,464 had higher affinity for the V-1a receptor compared to the OT receptor (8.5x more selective) with poor functional selectivity (2x selective for OT receptor agonism over V-1a receptor antagonism). Methylation of the resorcinol moiety (3) reversed the OT receptor pharmacological profile, removing agonist activity and inducing antagonist activity, without altering V-1a receptor pharmacology. All flexible tethered derivatives removed OT receptor affinity and activity resulting in the generation of highly selective V-1a receptor ligands. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.050
• 作为产物：
  描述：

  3,5-二羟基苯甲醛 、 N-Boc-哌嗪 在 溶剂黄146 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 73.0h， 以85%的产率得到4-(3,5-dihydroxy-benzyl)-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Piperazines as oxytocin agonists

  摘要：

  根据一般公式I揭示了具有OT激动剂活性的新化合物。

  公开号：

  EP1512687A1

文献信息

• Pyrazolo[1,4]diazepines as non-peptidic probes of the oxytocin and vasopressin receptors
  作者：Tristan A. Reekie、Iain S. McGregor、Michael Kassiou

  DOI：10.1016/j.tetlet.2014.06.022

  日期：2014.8

  An improved synthesis of differently substituted pyrazolo[1,4]diazepine compounds is reported. In addition, we have used this methodology to obtain non-peptidic compounds to probe the oxytocin and vasopressin receptors. (C) 2014 Elsevier Ltd. All rights reserved.
• PIPERAZINES AS OXYTOCIN AGONISTS
  申请人：Ferring B.V.

  公开号：EP1660501A2

  公开（公告）日：2006-05-31
• [EN] PIPERAZINES AS OXYTOCIN AGONISTS<br/>[FR] PIPERAZINES UTILISEES COMME AGONISTES DE L'OXYTOCINE
  申请人：FERRING BV

  公开号：WO2005023812A2

  公开（公告）日：2005-03-17

  Disclosed are novel compounds according to general formula (1), which have shown OT agonist activity.
• Piperazines as oxytocin agonists
  申请人：Ferring B.V.

  公开号：EP1512687A1

  公开（公告）日：2005-03-09

  Disclosed are novel compounds according to general formula I, which have shown OT agonist activity.

  根据一般公式I揭示了具有OT激动剂活性的新化合物。
• Flexible analogues of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin 1 a receptors
  作者：William T. Jorgensen、Damien W. Gulliver、Eryn L. Werry、Tristan Reekie、Mark Connor、Michael Kassiou

  DOI：10.1016/j.ejmech.2015.11.050

  日期：2016.1

  A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V-1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY -267,464 had higher affinity for the V-1a receptor compared to the OT receptor (8.5x more selective) with poor functional selectivity (2x selective for OT receptor agonism over V-1a receptor antagonism). Methylation of the resorcinol moiety (3) reversed the OT receptor pharmacological profile, removing agonist activity and inducing antagonist activity, without altering V-1a receptor pharmacology. All flexible tethered derivatives removed OT receptor affinity and activity resulting in the generation of highly selective V-1a receptor ligands. (C) 2015 Elsevier Masson SAS. All rights reserved.