ethyl 1,2,3,4-tetrahydro-4-(2,3,4-trimethoxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 1,2,3,4-tetrahydro-4-(2,3,4-trimethoxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
• 英文别名: ethyl 6-methyl-2-oxo-4-(2,3,4-trimethoxyphenyl)-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate；ethyl 6-methyl-2-oxo-4-(2,3,4-trimethoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 6-methyl-2-oxo-4-(2,3,4-trimethoxyphenyl)-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 化学式: C₁₇H₂₂N₂O₆
• 分子量: 350.371
• InChiKey: VDBNPSMWGYDJIC-UHFFFAOYSA-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：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  95.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  乙酰乙酸乙酯 、 尿素 、 2,3,4-三甲氧基苯甲醛 在 copper(II) nitrate trihydrate 作用下， 以85%的产率得到ethyl 1,2,3,4-tetrahydro-4-(2,3,4-trimethoxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
  参考文献：
  名称：

  2-Oxo-1,2,3,4-四氢嘧啶乙基酯作为有效的β-葡萄糖醛酸苷酶抑制剂：一锅法合成，体外和计算机研究

  摘要：

  背景：葡萄糖醛酸苷化对于有毒物质的代谢和排泄至关重要。β-葡萄糖醛酸苷酶减慢了葡萄糖醛酸化的过程，因此在大肠癌和许多其他疾病的发作中起重要作用。因此，抑制β-葡萄糖醛酸苷酶活性被认为是治疗几种疾病的重要方法。 目的：本研究旨在合成2-氧代-1,2,3,4-四氢嘧啶的文库，并评估其对β-葡萄糖醛酸苷酶的抑制活性及其酶的抑制方式。 方法：我们以三水合硝酸铜为催化剂，通过融合尿素，乙酰乙酸乙酯和各种醛类，合成了一系列的2-oxo-1,2,3,4-四氢嘧啶1-25。评价所有合成的化合物的体外β-葡萄糖醛酸苷酶抑制活性。此外，还使用MOE对接工具进行了分子对接研究。 结果：18种化合物显示出比标准的D-蔗糖1,4-内酯（一种众所周知的β-葡萄糖醛酸苷酶抑制剂（IC50 = 45.75±2.16 µM））更好的抑制活性。化合物20（IC50 = 1.36±0.03 µM）表现出优异的抑制活性，比标准品高出35倍。对接结果强调了2-化学-1

  DOI：

  10.2174/1573406414666180525105325

文献信息

• Xanthine Oxidase Inhibitory and Molecular Docking Studies on Pyrimidones
  作者：Humaira Zafar、Sarosh Iqbal、Sumaira Javaid、Khalid M. Khan、Muhammad I. Choudhary

  DOI：10.2174/1573406413666171129224919

  日期：2018.7.6

  Background: Xanthine oxidase is an important enzyme which catalyzes the production of uric acid and superoxide anion from xanthine. The over-production of these products leads to different disease conditions. For instance, uric acid is responsible for hyperuricemia, gout, and arthritis, while superoxide anion contributes to the oxidative stress, and related diseases. Hence XO is an important pharmacological target for the treatment of a range of diseases. Methods: Based on the structural resemblance of pyrimidines with xanthine, a series of previously synthesized ethyl 6- methyl-2-oxo-1, 2, 3, 4-tetrahydro-5-pyrimidinecarboxylate derivatives were evaluated for XO inhibitory activity. Results: Among 25 pyrimidone derivatives, 22 were found to be good to weak inhibitors with IC50 values in the range of 14.4 - 418 µM. Compounds 3, 14, 15, 18, and 21-23 were significant inhibitors, and thus analyzed for their kinetic parameters. Among them compounds 14, 15, 18, and 23 were competitive, 21 and 22 showed non-competitive, while 23 was a mixed-type of inhibitor. Molecular docking studies highlighted the interactions of these inhibitors with critical amino acids of XO, such as Val1011, Phe649, Lys771, and others. Moreover, the cytotoxicity studies on these selected inhibitors showed all these compounds to be non-cytotoxic. Conclusion: These non-cytotoxic, significant XO inhibitors can thus be further investigated for the treatment of hyperuricemia, and gout.

  背景：黄嘌呤氧化酶是催化黄嘌呤产生尿酸和超氧阴离子的一种重要酶。这些产物的过度产生会导致不同的疾病。例如，尿酸是高尿酸血症、痛风和关节炎的罪魁祸首，而超氧阴离子则会导致氧化应激和相关疾病。因此，XO 是治疗一系列疾病的重要药理靶点。 方法：根据嘧啶与黄嘌呤结构相似的特点，对之前合成的一系列 6-甲基-2-氧代-1，2，3，4-四氢-5-嘧啶羧酸乙酯衍生物的 XO 抑制活性进行了评估。 结果：在 25 种嘧啶酮衍生物中，有 22 种是良好至较弱的抑制剂，其 IC50 值在 14.4 - 418 µM 之间。化合物 3、14、15、18 和 21-23 具有显著的抑制作用，因此对其动力学参数进行了分析。分子对接研究强调了这些抑制剂与 XO 的关键氨基酸（如 Val1011、Phe649、Lys771 等）之间的相互作用。结论：因此，可以进一步研究这些无细胞毒性的 XO 重要抑制剂，以治疗高尿酸血症和痛风。
• 2-Oxo-1,2,3,4-tetrahydropyrimidines Ethyl Esters as Potent β- Glucuronidase Inhibitors: One-pot Synthesis, In vitro and In silico Studies
  作者：Sarosh Iqbal、Nimra N. Shaikh、Khalid M. Khan、Sehrish Naz、Zaheer Ul-Haq、Shahnaz Perveen、Muhammad I. Choudhary

  DOI：10.2174/1573406414666180525105325

  日期：2018.11.2

  addition, molecular docking studies were also performed by using MOE docking tools. Results: Eighteen compounds showed inhibitory activity better than the standard D-saccharic acid 1,4-lactone, a well known β-glucuronidase inhibitor (IC50 = 45.75 ± 2.16 µM). Compound 20 (IC50 = 1.36 ± 0.03 µM) showed an excellent inhibitory activity, thirty-five folds superior to the standard. Docking results highlighted

  背景：葡萄糖醛酸苷化对于有毒物质的代谢和排泄至关重要。β-葡萄糖醛酸苷酶减慢了葡萄糖醛酸化的过程，因此在大肠癌和许多其他疾病的发作中起重要作用。因此，抑制β-葡萄糖醛酸苷酶活性被认为是治疗几种疾病的重要方法。 目的：本研究旨在合成2-氧代-1,2,3,4-四氢嘧啶的文库，并评估其对β-葡萄糖醛酸苷酶的抑制活性及其酶的抑制方式。 方法：我们以三水合硝酸铜为催化剂，通过融合尿素，乙酰乙酸乙酯和各种醛类，合成了一系列的2-oxo-1,2,3,4-四氢嘧啶1-25。评价所有合成的化合物的体外β-葡萄糖醛酸苷酶抑制活性。此外，还使用MOE对接工具进行了分子对接研究。 结果：18种化合物显示出比标准的D-蔗糖1,4-内酯（一种众所周知的β-葡萄糖醛酸苷酶抑制剂（IC50 = 45.75±2.16 µM））更好的抑制活性。化合物20（IC50 = 1.36±0.03 µM）表现出优异的抑制活性，比标准品高出35倍。对接结果强调了2-化学-1
• A Highly Efficient and Green Catalytic Synthesis of 3,4-dihydro-pyrimidin-2-(1H)-ones (Thiones) Using 3-sulfonic Acid-1-imidazolopyridinium Hydrogen Sulfate under Solvent-free Conditions
  作者：Mohammad Bakherad、Mohaddeseh Javanmardi、Raheleh Doosti、Reza Tayebee

  DOI：10.5562/cca3013

  日期：——

  The ionic liquid catalyst 3-sulfonic acid-1-imidazolopyridinium hydrogen sulfate, [Simp]HSO4 was found to be a highly active and green catalyst for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones (thiones) under the solvent-free conditions. Avoiding organic solvents during the chemical reactions leading to an economic approach is effective. The reactions are characterized by high efficiency, short reaction time, high product yield, simple experimental procedure, availability of catalyst, and environmentally-friendly reaction conditions.