N-(adamant-1-yl)-3,7-dihydro-7-oxo-2,3-diphenyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide | 1388153-46-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N-(adamant-1-yl)-3,7-dihydro-7-oxo-2,3-diphenyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide
• 英文别名: N-(1-adamantyl)-10-oxo-2,3-diphenyl-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),11-tetraene-11-carboxamide
• CAS: 1388153-46-5
• 化学式: C₃₄H₃₂N₂O₃
• 分子量: 516.64
• InChiKey: ICUZNHDYUBYBGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  39
• 可旋转键数：
  4
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  diethyl 2-((2,3-dihydro-2,3-diphenylbenzo[b][1,4]oxazin-4-yl)-methylene)malonate 在 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.17h， 生成 N-(adamant-1-yl)-3,7-dihydro-7-oxo-2,3-diphenyl-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

文献信息

• 7-Oxo-[1,4]oxazino[2,3,4-<i>ij</i>]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists
  作者：Pier Giovanni Baraldi、Giulia Saponaro、Allan R. Moorman、Romeo Romagnoli、Delia Preti、Stefania Baraldi、Emanuela Ruggiero、Katia Varani、Martina Targa、Fabrizio Vincenzi、Pier Andrea Borea、Mojgan Aghazadeh Tabrizi

  DOI：10.1021/jm300763w

  日期：2012.7.26

  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.