(±)-ethyl 4-(furan-3-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate | 332026-77-4

• 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 4-(furan-3-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: 4-Furan-3-yl-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester；ethyl 4-(furan-3-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 332026-77-4
• 化学式: C₁₂H₁₄N₂O₄
• 分子量: 250.254
• InChiKey: KKTDAYOTVMBJGR-UHFFFAOYSA-N

物化性质

• 沸点：
  365.3±42.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为产物：
  描述：

  糠醛 、 乙酰乙酸乙酯 、 尿素 在 copper(II) bis(trifluoromethanesulfonate) 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以90%的产率得到(±)-ethyl 4-(furan-3-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  A microwave-assisted, copper-catalyzed three-component synthesis of dihydropyrimidinones under mild conditions

  摘要：

  The synthesis of dihydropyrimidinones via a clean multi-component Biginelli reaction under microwave irradiation is reported. The copper-catalyzed process proved to be simple, efficient, economical, and environmentally friendly. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.10.150

文献信息

• Concentrated solar radiation as a renewable heat source for a preparative-scale and solvent-free Biginelli reaction
  作者：Yatin U. Gadkari、Navnath T. Hatvate、Balaram S. Takale、Vikas N. Telvekar

  DOI：10.1039/d0nj01351j

  日期：——

  A well-known Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was performed in an environmentally responsible manner. Large numbers of substrates were screened, and found to give excellent yields of the desired products. In addition to the synthesis of drug molecules, the reaction was easily scaled up to 50 mmol. The present method was also energy efficient and saved

  以对环境负责的方式进行了众所周知的Biginelli反应，该反应用于合成3,4-二氢嘧啶-2（1 H）-酮/硫酮。筛选了大量的底物，发现得到所需产物的优异产率。除了合成药物分子外，该反应还容易扩大到50 mmol。与传统方法相比，本方法还具有能源效率，并节省了95％以上的能量。
• One-pot Synthesis of Dihydropyrimidinones Using Polyoxometalate Tri-supported Transition Metal Complexes
  作者：Razieh Fazaeli、Hamid Aliyan、Foroogh Mohammadifar、Amir Abbas Zamani、Mohammad Javad Bagi

  DOI：10.5012/jkcs.2011.55.4.666

  日期：2011.8.20

  Vanadium 치환체인 polyoxometalate 1, [Cu(2,2'-bipy)]$[Cu(2,2'-bipy)_2]_2[PMo_8V_6O_42}]\cdot}1.5H_2O$을 가지고 있는 inorganicorganic complex의 촉매 활성도를 Biginelli 반응에 적용하여 연구하였다. Dihydropyrimidinones를 one-pot 합성하는 반응에서, $H_3PMo_12}O_40}$ 촉매 보다[Cu(2,2'-bipy)]$[Cu(2,2'-bipy)_2]_2[PMo_8V_6O_42}]\cdot}1.5H_2O$ 촉매가 더 좋은 결과를 나타내었다. The catalytic activity of an inorganic-organic complex with a vanadium-substituted polyoxometalate 1, formulated as [Cu(2,2'-bipy)]$[Cu(2,2'-bipy)_2]_2[PMo_8V_6O_42}]\cdot}1.5H_2O$ was studied in the Biginelli reactions. The obtained results showed that, in the one-pot synthesis of dihydropyrimidinones, the turnover frequencies (TOF) for the [Cu(2,2'-bipy)]$[Cu(2,2'-bipy)_2]_2[PMo_8V_6O_42}]\cdot}1.5H_2O$ catalyst were higher than the $H_3PMo_12}O_40}$ catalyst.

  我们研究了一种具有钒取代聚金属氧酸盐1的无机有机复合材料的催化活性，化学式为[Cu(2,2'-bipy)]$[Cu(2,2'-bipy)_2]_2[PMo_8V_6O_42}]\cdot}1.5H_2O$，应用于Biginelli反应。在一锅合成二氢嘧啶酮的反应中，[Cu(2,2'-bipy)]$[Cu(2,2'-bipy)_2]_2[PMo_8V_6O_42}]\cdot}1.5H_2O$催化剂的周转频率（TOF）高于$H_3PMo_12}O_40}$催化剂。
• 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
• Discovery of 3,4-Dihydropyrimidin-2(1<i>H</i>)-ones As a Novel Class of Potent and Selective A_2B Adenosine Receptor Antagonists
  作者：Abel Crespo、Abdelaziz El Maatougui、Pierfrancesco Biagini、Jhonny Azuaje、Alberto Coelho、José Brea、María Isabel Loza、María Isabel Cadavid、Xerardo García-Mera、Hugo Gutiérrez-de-Terán、Eddy Sotelo

  DOI：10.1021/ml400185v

  日期：2013.11.14

  We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family of (nonzanthine) A(2B) receptor antagonists that exhibit an unusually high selectivity profile. The Biginelli-based hit optimization process enabled a thoughtful exploration of the structure-activity and structure-selectivity relationships for this chemotype, enabling the identification of ligands that combine structural simplicity with excellent hA(2B) AdoR affinity and remarkable selectivity profiles.