N-(adamantan-1-yl)-4-oxo-1-pentyl-6-(2-phenylethynyl)-1,4-dihydroquinoline-3-carboxamide | 1239604-31-9

• 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: N-(adamantan-1-yl)-4-oxo-1-pentyl-6-(2-phenylethynyl)-1,4-dihydroquinoline-3-carboxamide
• 英文别名: N-(1-adamantyl)-4-oxo-1-pentyl-6-(2-phenylethynyl)quinoline-3-carboxamide
• CAS: 1239604-31-9
• 化学式: C₃₃H₃₆N₂O₂
• 分子量: 492.661
• InChiKey: VOFUENNZZZQQMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(adamantan-1-yl)-6-iodo-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxamide 、 苯乙炔 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二异丙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以72%的产率得到N-(adamantan-1-yl)-4-oxo-1-pentyl-6-(2-phenylethynyl)-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 3. Synthesis, Structure−Affinity Relationships, and Pharmacological Characterization of 6-Substituted 4-Quinolone-3-carboxamides as Highly Selective Cannabinoid-2 Receptor Ligands

  摘要：

  A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting K(i) > 100 nM, all the quinolone-3-carboxamides 2 proved to be high affinity CB2 ligands, with K(i) values ranging from 73.2 to 0.7 nM and selectivity [SI = K(i)(CB1)/K(i)(CB2)] varying from > 14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI < 1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonist-like behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors.

  DOI：

  10.1021/jm100123x

文献信息

• Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 3. Synthesis, Structure−Affinity Relationships, and Pharmacological Characterization of 6-Substituted 4-Quinolone-3-carboxamides as Highly Selective Cannabinoid-2 Receptor Ligands
  作者：Serena Pasquini、Alessia Ligresti、Claudia Mugnaini、Teresa Semeraro、Lavinia Cicione、Maria De Rosa、Francesca Guida、Livio Luongo、Maria De Chiaro、Maria Grazia Cascio、Daniele Bolognini、Pietro Marini、Roger Pertwee、Sabatino Maione、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1021/jm100123x

  日期：2010.8.26

  A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting K(i) > 100 nM, all the quinolone-3-carboxamides 2 proved to be high affinity CB2 ligands, with K(i) values ranging from 73.2 to 0.7 nM and selectivity [SI = K(i)(CB1)/K(i)(CB2)] varying from > 14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI < 1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonist-like behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors.