(E)-6-(2,3,4-trimethoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione | 1173698-55-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (E)-6-(2,3,4-trimethoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-nitro-6-[(E)-2-(2,3,4-trimethoxyphenyl)ethenyl]-1H-pyrimidine-2,4-dione
• CAS: 1173698-55-9
• 化学式: C₁₅H₁₅N₃O₇
• 分子量: 349.3
• InChiKey: XLCVQBMKKZZSRI-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-甲基尿嘧啶 在 哌啶 、 硫酸 、 硝酸 作用下， 以 正丁醇 为溶剂， 生成 (E)-6-(2,3,4-trimethoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 5-Nitropyrimidine-2,4-dione Analogues as Inhibitors of Nitric Oxide and iNOS Activity

  摘要：

  Fifty two compounds based on 5‐nitropyrimidine‐2,4‐dione moiety have been synthesized and evaluated for their inhibitory potency on the production of nitric oxide. Among them, compound 36 inhibited the production of nitric oxide (IC50: 8.6 μm) on lipopolysaccharide‐induced RAW 264.7 cells and inducible nitric oxide synthase activity (IC50: 6.2 μm), as well as exerted no potential cytotoxicity (IC50 > 80.0 μm). Docking study confirmed that compound 36 was an inducible nitric oxide synthase inhibitor with perfect binding to the active site of inducible nitric oxide synthase. At a dose of 10 mg/kg, oral administration of 36 possessed protective properties in carrageenan‐induced paw edema of male ICR mice.

  DOI：

  10.1111/cbdd.12386

文献信息

• Discovery and Development of a Small Molecule Library with Lumazine Synthase Inhibitory Activity
  作者：Arindam Talukdar、Meghan Breen、Adelbert Bacher、Boris Illarionov、Markus Fischer、Gunda Georg、Qi-Zhuang Ye、Mark Cushman

  DOI：10.1021/jo900238q

  日期：2009.8.7

  (E)-5-Nitro-6-(2-hydroxystyryl)pyrimdine-2,4(1H,3H)-dione (9) was identified as a novel inhibitor of Schizosaccharomyces pombe lumazine synthase by high-throughput screening of a 100000 compound library. The K-i of 9 vs Mycobacterium tuberculosis lumazine synthase was 95 mu M. Compound 9 is a structural analogue of the lumazine synthase substrate 5-amino-6-(D-ribitylamino)-2,4-(1H,3H)pyrimidinedione (1). This indicates that the ribitylamino side chain of the substrate is not essential for binding to the enzyme. Optimization of the enzyme inhibitory activity through systematic structure modification of the lead compound 9 led to (E)-5-nitro-6-(4-nitrostyryl)pyrimidine-2,4(1H,3H)-dione (26), which has a K-i of 3.7 mu M vs M. tuberculosis lumazine synthase.

  (E)-5-硝基-6-(2-羟基丙二烯酰胺基)亚二噁嗪-2,4-(1H,3H)-双酮（编号9）通过对10万个化合物semble的高通量筛选，被识别为沙拉科斯角藻（Schizosaccharomyces pombe）亚胺合成都酶的新颖抑制剂。与结核菌（Mycobacterium tuberculosis）亚胺合成都酶的比结合位点（K_i）为95 μM。化合物9是亚胺合成都酶底物5-氨基-6-(D-inals-酰氨基)-2,4-(1H,3H)亚二噁嗪-双酮（编号1）的结构模拟物。这表明底物中的n-酰氨基侧链对酶的结合活性并非必不可少。通过系统修改第9号化合物的结构进行酶抑制活性优化，获得(E)-5-硝基-6-(4-硝基丙二烯酰胺基)亚二噁嗪-2,4-(1H,3H)-双酮（编号26）。其与结核菌亚胺合成都酶的比结合位点（K_i）为3.7 μM。