ethyl 2-amino-4-(4-hydroxy-3-methoxyphenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate | 359450-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: ethyl 2-amino-4-(4-hydroxy-3-methoxyphenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate
• CAS: 359450-51-4
• 化学式: C₁₅H₁₉N₃O₄
• 分子量: 305.334
• InChiKey: NVUCGQQERRUWNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  香草醛 、 乙酰乙酸乙酯 、 盐酸胍 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以77%的产率得到ethyl 2-amino-4-(4-hydroxy-3-methoxyphenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate
  参考文献：
  名称：

  2-氨基-1,4-二氢嘧啶作为多靶点抗菌配体的合成，体外潜力和计算研究

  摘要：

  在这项研究中，我们研究了含有2-氨基嘧啶骨架的小的多靶分子，它们可能进一步充当开发更有效的抗菌剂的前体。开发了一种有效的途径，通过使用超声辐射作为能源的2-氨基-1,4-二氢嘧啶。在计算机密度函数理论计算中表明，氯化锡介导的Biginelli反应生成2-氨基-1,4-二氢嘧啶具有在反应条件下相当容易获得的能量。计算的对各种细菌菌株的最低抑菌浓度表明，化合物3和11在金黄色葡萄球菌菌株中显示出与环丙沙星相当的体外活性，并且在大肠杆菌中的效价降低株。此外，为了了解有助于解释体外结果的作用机理，我们对合成化合物进行了计算机模拟ADMET分析。铅化合物3，6，和11被预测为具有可接受的药物动力学/药物样性质。通过数据挖掘和计算分析得出复合滥交现象。发现所有化合物对各种胺能G蛋白偶联受体，离子通道，激酶抑制剂，核受体配体，蛋白酶抑制剂和酶抑制剂均无底物。化合物3通过计算机结合不同的抗菌靶标进一步研究

  DOI：

  10.1007/s00044-016-1613-z

文献信息

• 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.