ethyl 3-(2-((diethoxyphosphoryl)methoxy)ethyl)-4-(4-hydroxyphenyl)-6-methyl-2-oxo-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 3-(2-((diethoxyphosphoryl)methoxy)ethyl)-4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 化学式: C₂₁H₃₁N₂O₈P
• 分子量: 470.46
• InChiKey: IOYAZXOAUKTUAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  32.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  123.63
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  4-(4-羟基苯基)-6-甲基-2-氧代-1,2,3,4-四氢嘧啶-5-羧酸乙酯 、 [(2-氯乙氧基)甲基]膦酸二乙酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以85%的产率得到ethyl 3-(2-((diethoxyphosphoryl)methoxy)ethyl)-4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  Design, Synthesis, <i>In Silico</i> and <i>In Vitro</i> Studies of Substituted 1, 2, 3, 4- Tetrahydro Pyrimidine Phosphorus Derivatives

  摘要：

  设计的两系列新型取代磷酸化的1,4-二氢吡啶和1,2,3,4-四氢嘧啶衍生物（4a-l，6a-l，9和10）与来自蜡样芽胞杆菌的DHFR、来自铜绿假单胞菌的LpxC、来自大肠杆菌的IDH和来自金黄色葡萄球菌的MurB的药物靶点进行分子对接研究，以促进其合成。这些化合物是由取代芳香醛、硫脲/尿素和乙酰乙酸乙酯在聚磷酸（PPA）的存在下合成的。随后，这些化合物与二乙基（2-氯乙氧基）甲基磷酸酯进行磷酸化以获得所需产品。针对指定细菌株的体外抗菌活性实验表明，在不同剂量浓度下具有良好的抑制活性。设计结构的定量构效关系（QSAR）描述符显示出它们令人满意的药物相似性。分子对接、QSAR描述符和体外抗菌活性实验的结果使得筛选出更安全且潜在的抗菌剂。化合物4a、4d、4i、6a、6d、9和10被发现是强效抗菌剂。

  DOI：

  10.2174/1386207318666150525093659

文献信息

• Design, synthesis, in silico, and in vitro evaluation of novel pyrimidine phosphonates with cytotoxicity against breast cancer cells
  作者：Nanda Kumar Yellapu、Navya Atluri、Kalpana Kandlapalli、Ravendra Babu Kilaru、Jhansi Rani Vangavaragu、Hariprasad Osuru、Nagaraju Chamarthi、P. V. G. K. Sarma、Bhaskar Matcha

  DOI：10.1007/s00044-013-0628-y

  日期：2014.1

  Pyrimidine derivatives are widely used for the treatment of breast cancer and rapid efforts are contributing to develop highly potential novel molecules. In view of this, in this study, novel pyrimidine phosphonate molecules were designed so as to inhibit aromatase, a potential target of breast cancer. Quantitative structure activity relationship descriptors were defined and they revealed that the molecules have an effective and safer drug-like properties, which also supported by absorption, distribution, metabolism, and excretion study. Molecular docking of these compounds into the aromatase active site revealed that they are showing strong interaction forming H-bonds and arene cationic interactions. The ligand-receptor complex of compound 6i showed a best docking score of -15.776 kcal/mol among all. Hence, this compound was synthesized and tested in vitro at different concentrations of 25, 50, 100, and 200 mu g/mL against MDA-MB-231 adenocarcinoma breast cancer cells and it exhibited excellent antiproliferative activity and also induced apoptosis. The results from in silico structure activity relationships, molecular docking study and in vitro assays suggesting the compound as a potential source of chemotherapeutic drug for the treatment and management of breast cancer.
• Design, Synthesis, &lt;i&gt;In Silico&lt;/i&gt; and &lt;i&gt;In Vitro&lt;/i&gt; Studies of Substituted 1, 2, 3, 4- Tetrahydro Pyrimidine Phosphorus Derivatives
  作者：Kilaru Babu、Yellapu Kumar、Aminedi Raghavendra、Venukadasula Phanindra、Golla Madhava、Nuchu Ravi、Matcha Bhaskar、Chamarthi Raju

  DOI：10.2174/1386207318666150525093659

  日期：2015.10.21

  Molecular docking studies of the designed two series (4a-l, 6a-l, 9 and 10) of novel substituted phosphorylated 1, 4-dihydropyridine and 1,2,3,4-tetrahydropyrimidine derivatives against the drug targets of DHFR from Bacillus cereus, LpxC from Pseudomonas aeruginosa, IDH from E. coli and MurB from Staphylococcus aureus were encouraged for their synthesis. These compounds were synthesized from substituted aromatic aldehydes, thiourea/urea and ethyl acetoacetate in the presence of polyphosphoric acid (PPA). These were further phosphorylated with diethyl (2-chloroethoxy) methyl phosphonate to get the desired products. In vitro anti-bacterial activity against the specified bacterial strains related to docked protein exhibited good inhibitory activity at different dose concentrations. Quantitative Structure Activity Relationship (QSAR) descriptors of the designed structures have demonstrated their satisfactory drug like properties. The results from Molecular Docking, QSAR descriptors and in vitro anti-bacterial activities led to the identification of safer and potential antibacterial agents of the title compounds screened. Compounds 4a, 4d, 4i, 6a, 6d, 9 and 10 were found to be potent antibacterial agents.

  设计的两系列新型取代磷酸化的1,4-二氢吡啶和1,2,3,4-四氢嘧啶衍生物（4a-l，6a-l，9和10）与来自蜡样芽胞杆菌的DHFR、来自铜绿假单胞菌的LpxC、来自大肠杆菌的IDH和来自金黄色葡萄球菌的MurB的药物靶点进行分子对接研究，以促进其合成。这些化合物是由取代芳香醛、硫脲/尿素和乙酰乙酸乙酯在聚磷酸（PPA）的存在下合成的。随后，这些化合物与二乙基（2-氯乙氧基）甲基磷酸酯进行磷酸化以获得所需产品。针对指定细菌株的体外抗菌活性实验表明，在不同剂量浓度下具有良好的抑制活性。设计结构的定量构效关系（QSAR）描述符显示出它们令人满意的药物相似性。分子对接、QSAR描述符和体外抗菌活性实验的结果使得筛选出更安全且潜在的抗菌剂。化合物4a、4d、4i、6a、6d、9和10被发现是强效抗菌剂。