3,7-dihydro-8-methyl-7-oxo-3-propyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid | 1388154-73-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3,7-dihydro-8-methyl-7-oxo-3-propyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid
• CAS: 1388154-73-1
• 化学式: C₁₆H₁₇NO₄
• 分子量: 287.315
• InChiKey: GCLPXMFEFFGJND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.74
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.53
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  金刚烷胺 、 3,7-dihydro-8-methyl-7-oxo-3-propyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid 在 N,N-二异丙基乙胺 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.17h， 以53%的产率得到N-(adamant-1-yl)-3,7-dihydro-8-methyl-7-oxo-3-propyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide
  参考文献：
  名称：

  7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists

  摘要：

  Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB2 receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2) K-i = 2.5 nM, SI = 166; 21, hCB(2) K-i = 0.81 nM, SI = 383; 38, hCB(2) K-i = 15.8 nM, SI > 633; 56, hCB(2) K-i = 8.12 nM, SI > 1231; (R)-58, hCB(2) K-i = 9.24 nM, SI > 1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB2 receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB2 receptor.

  DOI：

  10.1021/jm300763w
• 作为产物：
  描述：

  3,4-dihydro-6-methyl-3-propyl-2H-benzo[b][1,4]oxazine 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 3,7-dihydro-8-methyl-7-oxo-3-propyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid
  参考文献：
  名称：

  7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists

  摘要：

  Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB2 receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2) K-i = 2.5 nM, SI = 166; 21, hCB(2) K-i = 0.81 nM, SI = 383; 38, hCB(2) K-i = 15.8 nM, SI > 633; 56, hCB(2) K-i = 8.12 nM, SI > 1231; (R)-58, hCB(2) K-i = 9.24 nM, SI > 1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB2 receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB2 receptor.

  DOI：

  10.1021/jm300763w