(S)-tert-butyl 6-benzyl-4-(1,3-dioxoisoindolin-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate | 1426063-32-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-tert-butyl 6-benzyl-4-(1,3-dioxoisoindolin-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate
• 英文别名: tert-butyl (4S)-6-benzyl-4-(1,3-dioxoisoindol-2-yl)-3,4-dihydro-2H-quinoline-1-carboxylate
• CAS: 1426063-32-2
• 化学式: C₂₉H₂₈N₂O₄
• 分子量: 468.552
• InChiKey: DUGFLOUYVJZPDF-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  邻苯二甲酸亚胺 、 tert-butyl 6-benzyl-4-hydroxy-3,4-dihydroquinoline-1(2H)-carboxylate 在 三苯基膦 、 偶氮二甲酸二异丙酯 作用下， 以 四氢呋喃 为溶剂， 反应 24.67h， 生成 (S)-tert-butyl 6-benzyl-4-(1,3-dioxoisoindolin-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate 、 (R)-tert-butyl 6-benzyl-4-(1,3-dioxoisoindolin-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate
  参考文献：
  名称：

  Opioid Peptidomimetics: Leads for the Design of Bioavailable Mixed Efficacy μ Opioid Receptor (MOR) Agonist/δ Opioid Receptor (DOR) Antagonist Ligands

  摘要：

  We have previously described opioid peptidomimetic, 1, employing a tetrahydroquinoline scaffold and modeled on a series of cyclic tetrapeptide opioid agonists. We have recently described modifications to these peptides that confer a mu opioid receptor (MOR) agonist, delta opioid receptor (DOR) antagonist profile, which has been shown to reduce the development of tolerance to the analgesic actions of MOR agonists. Several such bifunctional ligands have been reported, but none has been demonstrated to cross the blood-brain barrier. Here we describe the transfer of structural features that evoked MOR agonist/DOR antagonist behavior in the cyclic peptides to the tetrahydroquinoline scaffold and show that the resulting peptidomimetics maintain the desired pharmacological profile. Further, the 4R diastereomer of 1 was fully efficacious and approximately equipotent to morphine in the mouse warm water tail withdrawal assay following intraperitoneal administration and thus a promising lead for the development of opioid analgesics with reduced tolerance.

  DOI：

  10.1021/jm400050y