4-butyl-N-[(2S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]-3-methylbutan-2-yl]benzamide | 1436378-49-2

• 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-butyl-N-[(2S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]-3-methylbutan-2-yl]benzamide
• CAS: 1436378-49-2
• 化学式: C₂₇H₃₉N₃O₂
• 分子量: 437.626
• InChiKey: NOZDSSGXLXTKNZ-HFZDXXHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  55.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-3-(2-methylpiperazin-1-yl)phenol 在 盐酸 、 硼烷四氢呋喃络合物 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 15.0h， 生成 4-butyl-N-[(2S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]-3-methylbutan-2-yl]benzamide
  参考文献：
  名称：

  Discovery of N-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

  摘要：

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.

  DOI：

  10.1021/jm400275h