8-(4-Ethoxy-phenyl)-1,3-dimethyl-5,6,7,8-tetrahydro-1H-1,3,4b,8,9-pentaaza-fluorene-2,4-dione

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 8-(4-Ethoxy-phenyl)-1,3-dimethyl-5,6,7,8-tetrahydro-1H-1,3,4b,8,9-pentaaza-fluorene-2,4-dione
• 英文别名: 9-(4-ethoxyphenyl)-1,3-dimethyl-7,8-dihydro-6H-purino[7,8-a]pyrimidine-2,4-dione
• 化学式: C₁₈H₂₁N₅O₃
• 分子量: 355.396
• InChiKey: XKJKPMFZGVERDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  70.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-(3-chloropropyl)-8-bromotheophylline 、 对乙氧基苯胺 以 various solvent(s) 为溶剂， 反应 5.0h， 以71%的产率得到8-(4-Ethoxy-phenyl)-1,3-dimethyl-5,6,7,8-tetrahydro-1H-1,3,4b,8,9-pentaaza-fluorene-2,4-dione
  参考文献：
  名称：

  Synthesis and biological activity of tricyclic aryloimidazo-, pyrimido-, and diazepinopurinediones

  摘要：

  Syntheses and physicochemical properties of N-aryl-substituted imidazo-, pyrimido-, and 1,3-diazepino[2,1-f]purinediones are described. These derivatives were synthesized by the cyclization of 7-haloalkyl-8-bromo-1,3-dimethyl- or 1,3-dipropyl-xanthine derivatives with corresponding arylamines. The obtained compounds (1-40), which can be envisaged as sterically fixed and configurationally stable analogs of 8-styrylxanthines, were evaluated for their affinity to adenosine A(1) and A(2A) receptors, the receptor subtypes that are predominant in the brain. Selected compounds were additionally investigated for affinity to the A(2B) and A(3) receptor subtypes. Many of the compounds showed adenosine A(2A) receptor affinity at micromolar or submicromolar concentrations and were A(2A)-selective, for example, compound 23 with p-fluoro substituent displayed K-i value of 0.147 mu M at the rat A2A receptor and more than 170-fold-A(2A) selectivity, compound 17 with naphthyl substituent had K-i value of 0.219 mu M and a more than 114-fold-A2A selectivity. The compounds were-somewhat weaker and less selective at the human receptor subtypes. Elongation of the dimethyl substituent to dipropyl in xanthine moiety improved affinity but reduced selectivity. 1,3-Dimethylimidazo-, pyrimido-, and diazepinopurinediones were evaluated in vivo as anticonvulsants in MES, ScMet, TTE tests and examined for neurotoxicity in mice (ip). Substances with pyrimido ring displayed protective activity in ScMet or in MES and ScMet tests, showing also neurotoxicity. The pyrimidine annelated ring is beneficial for both receptor affinity and anticonvulsant activity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.06.052

文献信息

• Synthesis and biological activity of tricyclic aryloimidazo-, pyrimido-, and diazepinopurinediones
  作者：Anna Drabczyńska、Christa E. Müller、Svenja K. Lacher、Britta Schumacher、Janina Karolak-Wojciechowska、Antony Nasal、Piotr Kawczak、Olga Yuzlenko、Elżbieta Pękala、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2006.06.052

  日期：2006.11

  Syntheses and physicochemical properties of N-aryl-substituted imidazo-, pyrimido-, and 1,3-diazepino[2,1-f]purinediones are described. These derivatives were synthesized by the cyclization of 7-haloalkyl-8-bromo-1,3-dimethyl- or 1,3-dipropyl-xanthine derivatives with corresponding arylamines. The obtained compounds (1-40), which can be envisaged as sterically fixed and configurationally stable analogs of 8-styrylxanthines, were evaluated for their affinity to adenosine A(1) and A(2A) receptors, the receptor subtypes that are predominant in the brain. Selected compounds were additionally investigated for affinity to the A(2B) and A(3) receptor subtypes. Many of the compounds showed adenosine A(2A) receptor affinity at micromolar or submicromolar concentrations and were A(2A)-selective, for example, compound 23 with p-fluoro substituent displayed K-i value of 0.147 mu M at the rat A2A receptor and more than 170-fold-A(2A) selectivity, compound 17 with naphthyl substituent had K-i value of 0.219 mu M and a more than 114-fold-A2A selectivity. The compounds were-somewhat weaker and less selective at the human receptor subtypes. Elongation of the dimethyl substituent to dipropyl in xanthine moiety improved affinity but reduced selectivity. 1,3-Dimethylimidazo-, pyrimido-, and diazepinopurinediones were evaluated in vivo as anticonvulsants in MES, ScMet, TTE tests and examined for neurotoxicity in mice (ip). Substances with pyrimido ring displayed protective activity in ScMet or in MES and ScMet tests, showing also neurotoxicity. The pyrimidine annelated ring is beneficial for both receptor affinity and anticonvulsant activity. (c) 2006 Elsevier Ltd. All rights reserved.