4-(((4-(((7-amino-2-(furan-2-yl)[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino)methyl)cyclohexyl)methyl)amino)-4-oxobutanoic acid | 1360053-08-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 4-(((4-(((7-amino-2-(furan-2-yl)[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino)methyl)cyclohexyl)methyl)amino)-4-oxobutanoic acid
• CAS: 1360053-08-2
• 化学式: C₂₀H₂₆N₈O₄
• 分子量: 442.478
• InChiKey: GBXLUZWRJNHJTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.56
• 重原子数：
  32.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  173.56
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  丁二酸酐 、 7-amino-5-(aminomethyl)cyclohexylmethylamino-2-(2-furyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine trifluoroacetate 在 吡啶 作用下， 反应 24.0h， 以80%的产率得到4-(((4-(((7-amino-2-(furan-2-yl)[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino)methyl)cyclohexyl)methyl)amino)-4-oxobutanoic acid
  参考文献：
  名称：

  A Novel Conjugated Agent between Dopamine and an A_2A Adenosine Receptor Antagonist as a Potential Anti-Parkinson Multitarget Approach

  摘要：

  We propose a potential antiparkinsonian prodrug DP-L-A(2A)ANT (2) obtained by amidic conjugation of dopamine (1) via a succinic spacer to a new triazolo-triazine A(2A) adenosine receptor (AR) antagonist A(2A)ANT (3). The affinity of 2 and its hydrolysis products-1, 3, dopamine-linker DP-L (4) and A(2A)ANT-linker L-A(2A)ANT (5)-was evaluated for hA(1), hA(2A), hA(2B) and hA(3) ARs and rat striatum A(2A)ARs or D-2 receptors. The hydrolysis patterns of 2, 4 and 5 and the stabilities of 1 and 3 were evaluated by HPLC analysis in human whole blood and rat brain homogenates. High hA(2A) affinity was shown by compounds 2 (K-i = 7.32 +/- 0.65 nM), 3 (K-i = 35 +/- 3 nM) and 5 (K-i = 72 +/- 5 nM), whose affinity values were similar in rat striatum. These compounds were not able to change dopamine affinity for D-2 receptors but counteracted the CGS 21680-induced reduction of dopamine affinity. DP-L (4) was inactive on adenosine and dopaminergic receptors. As for stability studies, compounds 4 and 5 were not degraded in incubation media. In human blood, the prodrug 2 was hydrolyzed (half-fife = 2.73 +/- 0.23 h) mainly on the amidic bound coupling the A(2A)ANT (3), whereas in rat brain homogenates the prodrug 2 was hydrolyzed (half-life > eight hours) exclusively on the amidic bound coupling dopamine, allowing its controlled release and increasing its poor stability as characterized by half-life = 22.5 +/- 1.5 min.

  DOI：

  10.1021/mp200489d