methyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate | 351063-18-8

• 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: methyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: methyl 4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 351063-18-8
• 化学式: C₁₃H₁₄N₂O₃S
• 分子量: 278.332
• InChiKey: CRTOFEQOGBLCGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  乙酰乙酸甲酯 、 间羟基苯甲醛 、 硫脲 在 C₂₀H₁₈N₂O₄Zr⁽²⁺⁾*2C₈F₁₇O₃S^(1-) 作用下， 以 neat (no solvent) 为溶剂， 反应 0.83h， 以90%的产率得到methyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  空气稳定的锆（IV）-三氯苯酚全氟辛烷磺酸盐是在无溶剂条件下合成3,4-二氢嘧啶-2-（1H）-酮/硫酮的高效且可重复使用的催化剂

  摘要：

  通过使Zr（salphen）Cl 2与C 8 F 17 SO 3 Ag反应成功合成了一种空气稳定的锆（IV）-salophen全氟辛烷磺酸盐（1）。配合物1通过不同的技术（NMR，IR，HRMS，TG-DSC，电导率和酸度测量）进行了表征和研究，被发现具有空气稳定性，耐水性，热稳定性和强路易斯酸性。络合物1在无溶剂条件下通过醛，1,3-二羰基化合物和脲/硫脲的Biginelli反应合成3,4-二氢嘧啶-2-（1H）-酮/硫酮具有很高的催化效率。此外，复数1可以重复使用5次，而催化效率的变化却很小。与以前报道的方法相比，该方案的重要特征是无溶剂条件，反应时间短，底物相容性广，效率高和可重复使用性好。

  DOI：

  10.1002/aoc.5454

文献信息

• The development of an ecofriendly procedure for alkaline metal (II) sulfate promoted synthesis of<i>N</i>,<i>N</i>′-dimethyl substituted (unsubstituted)-4-aryl-3,4-dihydropyrimidones (thiones) and corresponding bis-analogues in aqueous medium: Evaluation by green chemistry metrics
  作者：Chhanda Mukhopadhyay、Arup Datta

  DOI：10.1002/jhet.283

  日期：——

  Different alkaline metal (II) sulfates were used as catalysts for the N,N′-dimethyl substituted as well as unsubstituted 4-aryl-3,4-dihydropyrimidones (thiones) and their corresponding bis-analogues in aqueous medium. Among the various salts, MgSO4·7H2O (Epsom salt) proved to be the best catalyst giving the desired products in good to excellent yields. This catalyst enables the construction of a series

  在水性介质中，将不同的碱金属（II）硫酸盐用作N，N'-二甲基取代的和未取代的4-芳基-3,4-二氢嘧啶酮（硫酮）及其相应的双类似物的催化剂。在各种盐中，MgSO 4 ·7H 2 O（泻盐）被证明是最好的催化剂，以良好至极佳的收率提供了所需的产物。该催化剂能够构建一系列化合物库，特别是对于N，N'-二甲基取代的DHPM，其合成在文献中非常罕见。通过绿色化学的应用评估了在多种底物上的反应指标和非常好的相关性。J.杂环化​​学.2010。
• Synthesis of 1-alkyl triazolium triflate room temperature ionic liquids and their catalytic studies in multi-component Biginelli reaction
  作者：SANKARANARAYANAN NAGARAJAN、TANVEER M SHAIKH、ELANGO KANDASAMY

  DOI：10.1007/s12039-015-0919-6

  日期：2015.9

  as catalysts for convenient and high-yielding one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones and 3,4-dihydropyrimidin-2(1H)-thiones, which are Biginelli reaction products. Advantages of the methodology are operational convenience, short reaction times, avoidance of chromatographic purification and non-production of toxic waste. Further, the catalysts are easily recovered and reused without any

  三种基于布朗斯台德酸的离子液体的合成，即三氟甲磺酸1-乙基-1,2,4-三唑鎓（1a），三氟甲磺酸1-丙基-1,2,4-三唑鎓（1b）和1-丁基-1，描述了三氟甲磺酸2，4-三唑鎓（1c）。这些离子液体已用作Biginelli反应产物3,4-二氢嘧啶-2（1H）-酮和3,4-二氢嘧啶-2（1H）-硫酮的方便，高产率一锅合成的催化剂。 。该方法的优点是操作方便，反应时间短，避免色谱纯化和不产生有毒废物。此外，催化剂易于回收和再利用，而其催化活性没有任何明显的降低。 描述了室温下布朗斯台德酸基催化剂的合成及其作为方便和高产率一锅合成3,4二氢嘧啶-2（1H）-一的催化剂的实用性，这是Biginelli反应产物。催化剂可循环利用，而不会损失任何催化活性。
• Brønsted Acidic 1-Ethyl-1,2,4-Trizolium Phenylsulfonate as Catalyst for Biginelli Reaction
  作者：G. Puthukkudy、S. Nagarajan、E. Kandasamy

  DOI：10.14233/ajchem.2018.21373

  日期：——

  A Brønsted acidic 1-ethyl-1,2,4-triazolium phenylsulfonate has been synthesized and characterized. A catalytic study is performed for 1-ethyl-1,2,4-triazolium phenylsulfonate as acid catalyst for a multicomponent reaction of synthesis of series of 3,4-dihydropyrimidin-2(1H)-ones/thiones and their derivatives have been employed and the results were discussed in detail.

  合成了一种布氏酸性 1-乙基-1,2,4-三唑鎓苯磺酸盐，并对其进行了表征。研究人员采用 1-乙基-1,2,4-三唑鎓苯磺酸盐作为酸性催化剂，对合成一系列 3,4-二氢嘧啶-2(1H)-酮/硫离子及其衍生物的多组分反应进行了催化研究，并对结果进行了详细讨论。
• Design, synthesis, and in silico studies of tetrahydropyrimidine analogs as urease enzyme inhibitors
  作者：Nazli Ahangarzadeh、Neda Shakour、Sadaf Rezvanpoor、Hamid Bakherad、Mohammad H. Pakdel、Ghazaleh Farhadi、Saghi Sepehri

  DOI：10.1002/ardp.202200158

  日期：2022.10

  The urease enzyme, a metalloenzyme having Ni2+ ions, is recognized in some bacteria, fungi, and plants. Particularly, it is vital to the progress of infections induced by pathogenic microbes, such as Proteus mirabilis and Helicobacter pylori. Herein, we reported the synthesis of a series of tetrahydropyrimidine derivatives and evaluated their antiurease activity. Finally, quantitative and qualitative

  脲酶是一种具有Ni 2+离子的金属酶，在一些细菌、真菌和植物中被识别。特别是，它对于由奇异变形杆菌和幽门螺杆菌等病原微生物引起的感染的进展至关重要。在此，我们报道了一系列四氢嘧啶衍生物的合成并评估了它们的抗脲酶活性。最后，通过计算机研究对衍生物进行定量和定性分析。脲酶抑制活性测定为幽门螺杆菌的反应脲酶与不同浓度的化合物，硫脲用作标准化合物。应用对接和动力学方法来研究最佳化合物与活性位点中氨基酸的相互作用。所有化合物均表现出良好至优异的抗脲酶活性。强效化合物对 HUVEC 正常细胞系没有细胞毒性。根据对接研究，脲酶抑制活性最高的化合物4e (IC 50 = 6.81 ± 1.42 µM) 与脲酶活性位点的 Ni 2+离子形成 螯合物。此外，化合物4f与硫脲 (IC 50 = 22.03 ± 1.24 μM）。分子对接和动力学模拟结果与体外测定结果相关。此外，衍生物4a-n遵循 Lipinski
• Monastrol, a 3,4-dihydropyrimidin-2(1 H )-thione, as structural scaffold for the development of modulators for GHB high-affinity binding sites and α 1 β 2 δ GABA A receptors
  作者：Maria Damgaard、Anas Al-Khawaja、Mia Nittegaard-Nielsen、Rebekka F. Petersen、Petrine Wellendorph、Bente Frølund

  DOI：10.1016/j.ejmech.2017.06.024

  日期：2017.9

  The (alpha(4)beta delta subtype of the gamma-aminobutyric acid (GABA) type A receptors (GABA(A)Rs) has been shown to be implicated in high-affinity binding of the neuromodulator gamma-hydroxybutyric acid (GHB), but may not be the only GHB high-affinity binding sites. Monastrol has been identified as a modulator of GHB high affinity binding and is furthermore reported as an allosteric modulator selective for the alpha(1)beta(2)delta GABAARs. Therefore, structural determinants for selectivity at the two targets were investigated. 39 structural diverse monastrol analogues were synthesized by employing the Biginelli cyclocondensation and examined for modulation of GHB high-affinity binding using the GHB-specific ligand [H-3]NCS-382 [(E,RS)=6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid] in rat brain homogenate. Only limited modifications were allowed on the monastrol scaffold in order to maintain modulation of GHB high-affinity binding. However, three analogues of monastrol (11,12 and 24) enhanced the maximal binding of [H-3]NCS-382 to a higher maximal level than seen for monastrol itself. Selected compounds were further characterized as modulators at alpha(1)beta(2)delta, alpha(1)beta(2)gamma(2s) and alpha(1)beta(2) GABA(A)Rs. Most of these modulators were shown to have delta-specific GABA-potentiating effects. The dual effect shown for monastrol to modulate the GHB high-affinity binding and alpha(1)beta(2)delta GABA(A)R activity was also shown for the compounds 11, 18 and 24. Compound 29 displayed minimal modulatory effect on GABA(A)Rs and therefore appears to be a GHB high-affinity binding preferring modulator. However, compounds 34 and 37 were shown to be alpha(1)beta(2)delta GABA(A)R selective modulators, without modulatory effects on GHB high-affinity binding. Thus, our study shows that minor modifications in the structure of monastrol affects the selectivity profile for the two targets under study enabling separation of the dual activity. (C) 2017 Elsevier Masson SAS. All rights reserved.