8-cyclopentyl-3-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethyl)-1-propylxanthine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-cyclopentyl-3-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethyl)-1-propylxanthine
• 化学式: C₂₂H₃₂N₅O₃
• 分子量: 414.528
• InChiKey: ROQCRPVUAOXGQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  73.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(bromomethyl)-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrol-1-oxyl 在 ammonium sulfate 、 potassium carbonate 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 8-cyclopentyl-3-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethyl)-1-propylxanthine
  参考文献：
  名称：

  Development of Spin-Labeled Probes for Adenosine Receptors

  摘要：

  Functionalized xanthine derivatives bearing a nitroxide moiety at the 3- or 8-position were synthesized as electron paramagnetic resonance (EPR) probes. The 8-cyclopentyl-1-propylxanthine derivative 4, spin-labeled at N3 by substitution with a nitroxide-bearing dihydropyrrole moiety, was a potent and selective A(1) adenosine receptor antagonist (K-i for A(1) 5.5 nM, 1600-fold selectivity vs A(2A), > 200-fold vs A(2B), and 310-fold vs A(3) adenosine receptors). 8-(1-Oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)-1,3-dipropylxanthine 10 (K-i for A(1) 8.2 nM) was similarly potent and selective, while 8-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-1,3-dipropylxanthine 11 (K-i for A(1) 160 nM) exhibited significantly lower affinity for A(1) adenosine receptors. 8-[4-(((1-Oxyl-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-oxoethoxy)phenyl]-1-propylxanthine 14, a 3-unsubstituted xanthine derivative, was found to be a potent A(2B) adenosine receptor antagonist (K-i for A(2B) 48 nM) but also exhibited high affinity for A(1) receptors (K-i for A(1) 15.7 nM). An X-ray structure of compound 10 was obtained, confirming the proposed structure. The novel spin-labeled A(1)-selective or A(1)/A(2B)-nonselective adenosine receptor antagonists may become useful probes for biophysicochemical investigations of adenosine receptors in their membrane environment.

  DOI：

  10.1021/jm049513x

文献信息

• Development of Spin-Labeled Probes for Adenosine Receptors
  作者：Janez Ilaš、Slavko Pečar、Jörg Hockemeyer、Harald Euler、Armin Kirfel、Christa E. Müller

  DOI：10.1021/jm049513x

  日期：2005.3.1

  Functionalized xanthine derivatives bearing a nitroxide moiety at the 3- or 8-position were synthesized as electron paramagnetic resonance (EPR) probes. The 8-cyclopentyl-1-propylxanthine derivative 4, spin-labeled at N3 by substitution with a nitroxide-bearing dihydropyrrole moiety, was a potent and selective A(1) adenosine receptor antagonist (K-i for A(1) 5.5 nM, 1600-fold selectivity vs A(2A), > 200-fold vs A(2B), and 310-fold vs A(3) adenosine receptors). 8-(1-Oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)-1,3-dipropylxanthine 10 (K-i for A(1) 8.2 nM) was similarly potent and selective, while 8-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-1,3-dipropylxanthine 11 (K-i for A(1) 160 nM) exhibited significantly lower affinity for A(1) adenosine receptors. 8-[4-(((1-Oxyl-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-oxoethoxy)phenyl]-1-propylxanthine 14, a 3-unsubstituted xanthine derivative, was found to be a potent A(2B) adenosine receptor antagonist (K-i for A(2B) 48 nM) but also exhibited high affinity for A(1) receptors (K-i for A(1) 15.7 nM). An X-ray structure of compound 10 was obtained, confirming the proposed structure. The novel spin-labeled A(1)-selective or A(1)/A(2B)-nonselective adenosine receptor antagonists may become useful probes for biophysicochemical investigations of adenosine receptors in their membrane environment.