ethyl 1-benzyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-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-benzyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: 1-benzyl-5-(ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one；ethyl 3-benzyl-4-methyl-2-oxo-6-phenyl-1,6-dihydropyrimidine-5-carboxylate
• 化学式: C₂₁H₂₂N₂O₃
• 分子量: 350.417
• InChiKey: OTTYPLCWASEQQI-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：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-甲基苯磺酸苯基甲基酯 、 6-甲基-2-氧代-4-苯基-1,2,3,4-四氢-5-嘧啶羧酸乙酯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以75%的产率得到ethyl 1-benzyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  Regioselective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones: Screening of their biological activities against Ca2+-ATPase

  摘要：

  A regioselective N1-alkylation of 3,4-dihydropyrimidin-2(1H)-ones using a very efficient mild base Cs2CO3 and alkyl halides at room temperature has been reported. The selectivity of this methodology is excellent and the yields of the alkylated products are very good. Furthermore inhibitory action of both the 3,4-dihydropyrimidin-2(1H)-ones and the N1-alkylated derivatives were tested on Ca2+-ATPase, which revealed that the parent compounds can act as Ca2+-ATPase inhibitors whereas the N1-alkylated derivatives are inefficient for this purpose. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.043

文献信息

• Selective N1-Alkylation of 3,4-Dihydropyrimidin-2(1<i>H</i>)-ones Using Mitsunobu-Type Conditions
  作者：C. Oliver Kappe、Doris Dallinger

  DOI：10.1055/s-2002-34881

  日期：——

  The regioselective N1-alkylation of 3,4-dihydropyrimidin-2(1H)-ones via Mitsunobu reaction is reported. Using the highly reactive Mitsunobu coupling reagent combination N,N,N′,N′-tetramethylazodicarboxamide/tributylphosphine (TMAD-TBP) and a set of primary alcohols a small library of N1-alkylated dihydropyrimidones is obtained in good to excellent yields.

  报道了通过 Mitsunobu 反应实现 3,4-二氢嘧啶-2(1H)-酮的 N1-烷基选择性烷基化。使用高活性的 Mitsunobu 偶联试剂组合 N,N,N',N'-四甲基偶氮二羧酰胺/三丁基膦（TMAD-TBP）以及一系列伯醇，获得了产率良好至优异的一系列 N1-烷基化二氢嘧啶酮的小型化合物库。
• Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines
  作者：Fatima Iftikhar、Farhana Yaqoob、Nida Tabassum、Muhammad Saeed Jan、Abdul Sadiq、Saba Tahir、Tahira Batool、Basit Niaz、Farzana Latif Ansari、Muhammad Iqbal Choudhary、Umer Rashid

  DOI：10.1016/j.bioorg.2018.05.026

  日期：2018.10

  anti-angiogenesis compound in a CAM assay. Docking studies were also performed with Molecular Operating Environment (MOE) to further analyse the mode of inhibition of these compounds. Binding mode analysis of the most active inhibitors showed that these are well accommodated into the binding site of enzyme though stable hydrogen bonding and hydrophobic interactions.

  胸苷磷酸化酶（TP）是一种血管生成酶。它在血管生成，肿瘤生长，侵袭和转移中起重要作用。在当前的研究工作中，我们研究了二氢嘧啶-2-酮（DHPM-2-ones）的结构修饰对TP抑制的影响。通过在C-6位的结构修饰，设计并合成了一系列十八个3,4-二氢嘧啶-2-酮新衍生物。然后评估所有这些新的衍生物对大肠杆菌中胸苷磷酸化酶（TP）的体外抑制。恶二唑衍生物4a-e在低微摩尔浓度下表现出优异的TP抑制作用，优于标准药物7-地塞黄嘌呤（7-DX）。在所有这些化合物中，4b被发现是最有效的，IC 50  = 1.09±0.004μM。还通过绒毛膜尿囊膜（CAM）测定法研究了代表性化合物的抗血管生成潜力。同样，在CAM测定中，发现化合物4b是有效的抗血管生成化合物。还使用分子操作环境（MOE）进行了对接研究，以进一步分析这些化合物的抑制方式。对最具活性的抑制剂的结合模式分析表明，尽管它们具有稳定的氢键结
• Polyphosphate Ester-Mediated Synthesis of Dihydropyrimidines. Improved Conditions for the Biginelli Reaction
  作者：C. Oliver Kappe、S. Fabio Falsone

  DOI：10.1055/s-1998-1764

  日期：1998.7

  Dihydropyrimidines 7 are prepared in high yield by a one-pot condensation of aldehydes, acetoacetates, and ureas using a polyphosphate ester-mediated cyclocondensation reaction. Yields are significantly higher than utilizing classical Biginelli reaction conditions.

  二氢嘧啶7通过醛、乙酰乙酸酯和脲在一锅法中使用聚磷酸酯介导的环缩合反应，以高产率制备。与传统的Biginelli反应条件相比，产率显著提高。
• Structure based medicinal chemistry-driven strategy to design substituted dihydropyrimidines as potential antileishmanial agents
  作者：Umer Rashid、Riffat Sultana、Nargis Shaheen、Syed Fahad Hassan、Farhana Yaqoob、Muhammad Jawad Ahmad、Fatima Iftikhar、Nighat Sultana、Saba Asghar、Masoom Yasinzai、Farzana Latif Ansari、Naveeda Akhter Qureshi

  DOI：10.1016/j.ejmech.2016.03.022

  日期：2016.6

  In an attempt to explore novel and more potent antileishmanial compounds to diversify the current inhibitors, we pursued a medicinal chemistry-driven strategy to synthesize novel scaffolds with common pharmacophoric features of dihydropyrimidine and chalcone as current investigational antileishmanial compounds. Based on the reported X-ray structure of Pteridine reductase 1 (PTR1) from Leishmania major

  为了探索新型和更有效的抗风白蚁化合物以使目前的抑制剂多样化，我们采用了药物化学驱动的策略来合成具有二氢嘧啶和查耳酮的共同药理学特征的新型支架，作为目前研究的抗风白蚁化合物。基于报道的来自利什曼原虫（Leishmania major）的蝶啶还原酶1（PTR1）的X射线结构，我们设计了许多基于二氢嘧啶的衍生物，以在PTR1活性位点进行特异性相互作用。我们的先导化合物8i对L. Major和Leishmania donovani的前鞭毛体显示出有效的体外抗疟药活性，IC50值分别为0.47杯/毫升和1.5杯/毫升。出色的体外活性最终表明，我们的先导化合物足以根除内脏和局部利什曼病。此外，还进行了对接分析和计算机模拟ADMET。预测的分子特性支持了我们的实验分析，即这些化合物具有消除内脏和局部利什曼病的潜力。
• Structure based virtual screening-driven identification of monastrol as a potent urease inhibitor
  作者：Umer Rashid、Iram Batool、Abdul Wadood、Ajmal Khan、Zaheer ul-Haq、Muhammad Iqbal Chaudhary、Farzana Latif Ansari

  DOI：10.1016/j.jmgm.2013.04.006

  日期：2013.6

  Virtual screening uses computer based methods to discover new ligands on the basis of biological structures. Among all virtual screening methods structure based docking has received considerable attention. In an attempt to identify new ligands as urease inhibitors, structure-based virtual screening (SBVS) of an in-house database of 10,000 organic compounds was carried out. The X-ray crystallographic structure of Bacillus pasteurii (BP) in complex with acetohydroxamic acid (PDB Code 4UBP) was used as a protein structure. As a starting point, similar to 10,000 compounds of our in-house database were analyzed to check redundancy and the compounds found repeated were removed from the database. Finally 6993 compounds were docked into the active site of BP urease using GOLD and MOE-Dock software. A remarkable feature of this study was the identification of monastrol, a well-known KSP inhibitor already in clinical trials, as a novel urease inhibitor. The hits identified were further evaluated by molecular docking and on examination of the affinity predictions, twenty-seven analogs of monastrol were synthesized by a multicomponent Biginelli reaction followed by their in vitro screening as urease inhibitors. Finally twelve compounds were identified as new urease inhibitors. The excellent in vitro activity suggested that these compounds may serve as viable lead compounds for the treatment of urease related problems. (c) 2013 Elsevier Inc. All rights reserved.