6-amino-5-[2-(4-isobutylphenyl)propanoyl]amino-1,3-dimethyl-1H-pyrimidine-2,6-dione | 872051-97-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 6-amino-5-[2-(4-isobutylphenyl)propanoyl]amino-1,3-dimethyl-1H-pyrimidine-2,6-dione
• 英文别名: N-(6-Amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)-2-(4-isobutylphenyl)propanamide；N-(4-amino-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)-2-[4-(2-methylpropyl)phenyl]propanamide
• CAS: 872051-97-3
• 化学式: C₁₉H₂₆N₄O₃
• 分子量: 358.44
• InChiKey: UKINSTUMXZFZIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  95.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-amino-5-[2-(4-isobutylphenyl)propanoyl]amino-1,3-dimethyl-1H-pyrimidine-2,6-dione 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以67.4%的产率得到8-[1-(4-isobutylphenyl)ethyl]-1,3-dimethyl-3,7-dihydropurin-2,6-dione
  参考文献：
  名称：

  New 8-substituted xanthiene derivatives as potent bronchodilators

  摘要：

  The synthesis and structure determination of 8-aryl /alkyl aryl 1, 3-dimethyl-3, 7-dihydropurin-2, 6-dione derivatives (1-13), was carried out in this study. Bronchodilator activity is investigated using isolated guinea-pig tracheal strips, pre-contracted by acetylcholine and histamine. Spasmolytic activity of the compounds was compared to theophylline. Synthesized compounds (1-13) did not inhibit the acetylcholine-induced pre-contractions except compound (8) at 10(-5) M concentration. In contrast, some of the compounds, especially (7), (11), (12) at 10(-5) M and (3), (4), (9) and (11) in 10(-4) M displayed inhibitory activity on the tracheal strips pre-contracted by histamine. The potency of the compounds at human adenosine receptors was evaluated using radioligand binding assay and a cyclic AMP functional assay in CHO cells expressing these receptors. Compound (11) displayed the greatest activity against radioligand binding of specific agonists to A2A and A2B receptors. The compounds were relatively selective for both A2A and A2B compared with A1 and A3 receptors. All compounds were also tested for the inhibition of NECA-induced cAMP accumulation mediated by the A2B adenosine receptor and compound (11) was found to be the most effective. Our results showed that these compounds are acting as selective adenosine antagonists, especially for adenosine A2B receptors, and are promising as potent anti-inflammatory agents rather than bronchodilator for the treatment of asthma.

  DOI：

  10.1016/j.farmac.2005.08.011
• 作为产物：
  描述：

  5,6-二氨基-1,3-二甲基脲嘧啶 、 布洛芬 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 24.0h， 以71.3%的产率得到6-amino-5-[2-(4-isobutylphenyl)propanoyl]amino-1,3-dimethyl-1H-pyrimidine-2,6-dione
  参考文献：
  名称：

  New 8-substituted xanthiene derivatives as potent bronchodilators

  摘要：

  The synthesis and structure determination of 8-aryl /alkyl aryl 1, 3-dimethyl-3, 7-dihydropurin-2, 6-dione derivatives (1-13), was carried out in this study. Bronchodilator activity is investigated using isolated guinea-pig tracheal strips, pre-contracted by acetylcholine and histamine. Spasmolytic activity of the compounds was compared to theophylline. Synthesized compounds (1-13) did not inhibit the acetylcholine-induced pre-contractions except compound (8) at 10(-5) M concentration. In contrast, some of the compounds, especially (7), (11), (12) at 10(-5) M and (3), (4), (9) and (11) in 10(-4) M displayed inhibitory activity on the tracheal strips pre-contracted by histamine. The potency of the compounds at human adenosine receptors was evaluated using radioligand binding assay and a cyclic AMP functional assay in CHO cells expressing these receptors. Compound (11) displayed the greatest activity against radioligand binding of specific agonists to A2A and A2B receptors. The compounds were relatively selective for both A2A and A2B compared with A1 and A3 receptors. All compounds were also tested for the inhibition of NECA-induced cAMP accumulation mediated by the A2B adenosine receptor and compound (11) was found to be the most effective. Our results showed that these compounds are acting as selective adenosine antagonists, especially for adenosine A2B receptors, and are promising as potent anti-inflammatory agents rather than bronchodilator for the treatment of asthma.

  DOI：

  10.1016/j.farmac.2005.08.011

文献信息

• New 8-substituted xanthiene derivatives as potent bronchodilators
  作者：Barkın Berk、Hülya Akgün、Kevser Erol、Başar Sırmagül、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1016/j.farmac.2005.08.011

  日期：2005.11

  The synthesis and structure determination of 8-aryl /alkyl aryl 1, 3-dimethyl-3, 7-dihydropurin-2, 6-dione derivatives (1-13), was carried out in this study. Bronchodilator activity is investigated using isolated guinea-pig tracheal strips, pre-contracted by acetylcholine and histamine. Spasmolytic activity of the compounds was compared to theophylline. Synthesized compounds (1-13) did not inhibit the acetylcholine-induced pre-contractions except compound (8) at 10(-5) M concentration. In contrast, some of the compounds, especially (7), (11), (12) at 10(-5) M and (3), (4), (9) and (11) in 10(-4) M displayed inhibitory activity on the tracheal strips pre-contracted by histamine. The potency of the compounds at human adenosine receptors was evaluated using radioligand binding assay and a cyclic AMP functional assay in CHO cells expressing these receptors. Compound (11) displayed the greatest activity against radioligand binding of specific agonists to A2A and A2B receptors. The compounds were relatively selective for both A2A and A2B compared with A1 and A3 receptors. All compounds were also tested for the inhibition of NECA-induced cAMP accumulation mediated by the A2B adenosine receptor and compound (11) was found to be the most effective. Our results showed that these compounds are acting as selective adenosine antagonists, especially for adenosine A2B receptors, and are promising as potent anti-inflammatory agents rather than bronchodilator for the treatment of asthma.