5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-imine

• 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: 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-imine
• 英文别名: ethyl 2-amino-6-methyl-4-phenyl-1,4-dihydropyrimidine-5-carboxylate
• 化学式: C₁₄H₁₇N₃O₂
• 分子量: 259.308
• InChiKey: DSISVHMNQRQRHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-imine 在 sodium acetate 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙酸酐 为溶剂， 反应 5.0h， 生成 6-ethoxycarbonyl-2,7-dimethyl-5-phenyl-1,5-dihydroimidazo[1,2-a]pyrimidin-3(2H)-one
  参考文献：
  名称：

  高效降压药，恶唑/噻唑-[3,2-a]-嘧啶-3（2H）-和1,5-二氢咪唑-[1,2-a]-嘧啶-3的药效学建模，设计和合成（2H）-一阶导数：试行

  摘要：

  改进的药效团模型，分子特性，几何分析和SAR合成了恶唑/噻唑-[3,2-a]-嘧啶-3（2H）-one和1,5-二氢咪唑-[1,2-a] ] -pyrimidin-3（2H）-one衍生物具有有效的抗高血压活性。6-乙氧基羰基-2,7-二甲基-5-苯基-1,5-二氢咪唑并[3,2-a]嘧啶-3（2H）-one（4g）和6-乙氧基羰基-2,7-二甲基- 5-（3-甲基-苯基）-1,5-二氢咪唑并[3,2-a]嘧啶-3（2H）-one（4h）分别显示，在1.5毫克/千克体重的剂量下，平均动脉血压（MABP，mm / Hg）在6和12小时内分别降低了79.78％和92.95％，而在3.0毫克/千克体重下-与标准药物硝苯地平相比，在体重减轻的情况下，在6小时和12小时内MABP分别降低了95.46％和92.02％。

  DOI：

  10.1016/j.bmcl.2020.127604
• 作为产物：
  描述：

  6-甲基-2-氧代-4-苯基-1,2,3,4-四氢-5-嘧啶羧酸乙酯 在 三氯氧磷 作用下， 生成 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-imine
  参考文献：
  名称：

  Researches on Pyrimidines. CXXXIII. Some Reactions and Derivatives of 2-Keto-4-phenyl-5-carbethoxy-6-methyl-1,2,3,4-tetrahydropyrimidine

  摘要：

  DOI：

  10.1021/ja01334a043

文献信息

• One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
  作者：Jessica Bais、Fabio Benedetti、Federico Berti、Iole Cerminara、Sara Drioli、Maria Funicello、Giorgia Regini、Mattia Vidali、Fulvia Felluga

  DOI：10.3390/molecules25184152

  日期：——

  A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC50 in the range 100 nM–50 μM.

  通过使用不同的醛与β-二羰基化合物和尿素的“一锅法”三组分Biginelli反应合成了一系列二氢嘧啶酮类化合物。选择性地，也从硫脲和盐酸胍得到了2-硫氧代和2-亚氨基类似物。这些产物在体外被筛选，用于评估它们的β-分泌酶抑制活性。大多数化合物表现出活性，IC50在100 nM至50 μM范围内。
• Synthesis, in vitro potential and computational studies on 2-amino-1, 4-dihydropyrimidines as multitarget antibacterial ligands
  作者：Muhammad Jawad Ahmad、Syed Fahad Hassan、Riffat Un Nisa、Khurshid Ayub、Muhammad Shahid Nadeem、Samina Nazir、Farzana Latif Ansari、Naveeda Akhtar Qureshi、Umer Rashid

  DOI：10.1007/s00044-016-1613-z

  日期：2016.9

  acceptable pharmacokinetic/drug-like properties. Data mining and computational analysis were employed to derive compound promiscuity phenomenon. All the compounds were found nonsubstrate towards various aminergic G-protein coupled receptors, ion-channels, kinase inhibitor, nuclear receptor ligand, protease inhibitor, and enzyme inhibitor. Compound 3 was further investigated by in silico binding to different

  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
• Efficient Biginelli Synthesis of 2-Aminodihydropyrimidines under Microwave Irradiation
  作者：Fulvia Felluga、Fabio Benedetti、Federico Berti、Sara Drioli、Giorgia Regini

  DOI：10.1055/s-0036-1591900

  日期：2018.5

  A practical and general method for the Biginelli cyclocondensation of guanidine with aldehydes and β-dicarbonyl compounds is described and illustrated with the synthesis of a set of 26 functionalized 2-amino-3,4-dihydropyrimidines. The simple protocol involves the ­microwave-mediated reaction of a twofold excess of guanidine hydrochloride with the required reaction partners in an alcohol at 120 °C

  用一组 26 个功能化的 2-氨基-3,4-二氢嘧啶的合成描述和说明了胍与醛和 β-二羰基化合物的 Biginelli 环缩合反应的实用和通用方法。简单的协议涉及双倍过量的盐酸胍与所需的反应伙伴在 120 °C 的酒精中的微波介导反应。收率通常良好，反应时间短，后处理简单。其范围比在常规加热下进行的类似反应要广泛得多。
• An improved synthesis of Biginelli-type compounds via phase-transfer catalysis
  作者：Bahar Ahmed、Riaz A. Khan、Habibullah、Manoj Keshari

  DOI：10.1016/j.tetlet.2009.03.177

  日期：2009.6

  3,4-Dihydropyrimidin-2(1H)-one, 3,4-dihydropyrimidin-2(1H)-thione, and 3,4-dihydropyrimidin-2(1H)-imine derivatives were synthesized by modified Biginelli cyclocondensation reaction in a time-efficient manner with near quantitative yields starting from appropriately substituted aromatic aldehyde, β-ketoester and either urea, thiourea or guanidine as constituent synthons using tetra-butyl ammonium bromide

  通过改进的Biginelli环缩合反应合成了3,4-二氢嘧啶-2（1 H）-一，3,4-二氢嘧啶-2（1 H）-硫酮和3,4-二氢嘧啶-2（1 H）-亚胺衍生物。首次以四丁基溴化铵（TBAB）为催化剂，以适当的取代芳族醛，β-酮酸酯和尿素，硫脲或胍作为构成合成子的高效方式，以近乎定量的产率获得了收率。
• Controllable selectivity in Biginelli and Hantzsch reactions using nanoZnO as a structure base catalyst
  作者：Fatemeh Tamaddon、Somayeh Moradi

  DOI：10.1016/j.molcata.2012.12.005

  日期：2013.4

  Preparative nanoZnO and ZnO have been found as reusable catalysts for either condensation or dissociation of urea to ammonia and controllable selectivity in the Biginelli and Hantzsch reactions. The feasibility of urea dissociation to ammonia and switching of the selectivity of heterocyclization for DHPMs to DHPs over various metal oxides has been comparatively investigated. In the presence of nanoZnO and ZnO, direction of the MCR reaction in either Biginelli or Hantzsch way is possible by choice of the reaction conditions. Biginelli reaction occurs at 60 degrees C under solvent-free conditions, while Hantzsch reaction occurs in water at similar to 120-140 degrees C or under microwave irradiation using 5 mol% nanoZnO or 10 mol% ZnO. (C) 2012 Elsevier B.V. All rights reserved.