6-amino-5-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)carboxamido-1,3-dipropyluracil

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 6-amino-5-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)carboxamido-1,3-dipropyluracil
• 化学式: C₁₉H₃₀N₅O₄
• 分子量: 392.478
• InChiKey: LAYPKPWEDOECKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-amino-5-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)carboxamido-1,3-dipropyluracil 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.75h， 以75%的产率得到8-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)-1,3-dipropylxanthine
  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
• 作为产物：
  描述：

  5,6-二氨基-1,3-二丙基嘧啶-2,4(1H,3H)-二酮 、 3-carboxy-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrol-1-yloxy 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以67%的产率得到6-amino-5-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)carboxamido-1,3-dipropyluracil
  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.