ethyl 4-(3,4-dihydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate | 326870-62-6

• 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 4-(3,4-dihydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: Ethyl 4-(3,4-dihydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate；ethyl 4-(3,4-dihydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 326870-62-6
• 化学式: C₁₄H₁₆N₂O₄S
• 分子量: 308.358
• InChiKey: JRBBYQDOWHPACZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 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：
  123
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-(3,4-dihydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 吗啉 、 吡啶 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 ethyl (Z)-5-(3,4-dihydroxyphenyl)-7-methyl-2-(4-morpholinobenzylidene)-3-oxo-3,5-dihydro-2H-thiazolo[3,2-a]pyrimidine-6-carboxylate
  参考文献：
  名称：

  急性肺损伤中具有抗炎活性的噻唑并[3,2-a]嘧啶衍生物的设计，合成及构效关系分析。

  摘要：

  急性肺损伤（ALI）的致死率很高，白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）在ALI病例中对组织恶化的影响最大。在这项研究中，我们基于先前鉴定的先导化合物设计并合成了一系列新的噻唑并[3,2-a]嘧啶衍生物，并评估了它们的抗炎活性。结构-活性关系研究导致发现了两种高效抑制剂。发现这两种有前途的化合物以剂量依赖性方式抑制小鼠原发性腹膜巨噬细胞（MPM）中脂多糖（LPS）诱导的IL-6和TNF-α释放。此外，这些化合物的施用导致肺组织病理学改善并且在体内减弱了LPS诱导的ALI。综上所述，这些数据表明这些新颖的噻唑罗[3，

  DOI：

  10.1002/cmdc.201700175
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 硫脲 、 3,4-二羟基苯甲醛 在 氨基磺酸 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 ethyl 4-(3,4-dihydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  急性肺损伤中具有抗炎活性的噻唑并[3,2-a]嘧啶衍生物的设计，合成及构效关系分析。

  摘要：

  急性肺损伤（ALI）的致死率很高，白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）在ALI病例中对组织恶化的影响最大。在这项研究中，我们基于先前鉴定的先导化合物设计并合成了一系列新的噻唑并[3,2-a]嘧啶衍生物，并评估了它们的抗炎活性。结构-活性关系研究导致发现了两种高效抑制剂。发现这两种有前途的化合物以剂量依赖性方式抑制小鼠原发性腹膜巨噬细胞（MPM）中脂多糖（LPS）诱导的IL-6和TNF-α释放。此外，这些化合物的施用导致肺组织病理学改善并且在体内减弱了LPS诱导的ALI。综上所述，这些数据表明这些新颖的噻唑罗[3，

  DOI：

  10.1002/cmdc.201700175

文献信息

• Nanometasilica disulfuric acid (NMSDSA) and nanometasilica monosulfuric acid sodium salt (NMSMSA) as two novel nanostructured catalysts: applications in the synthesis of Biginelli-type, polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives
  作者：Mohammad Ali Zolfigol、Hossein Ghaderi、Saeed Baghery、Leila Mohammadi

  DOI：10.1007/s13738-016-0964-1

  日期：2017.1

  synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives via one-pot three-component condensation reaction between several aldehydes, ethyl acetoacetate and urea or thiourea. To further study catalytic properties of NMSDSA and NMSMSA, they were used in the synthesis of polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives under same reaction conditions. NMSDSA and NMSMSA have advantages such

  摘要设计，合成了纳米金属二硫酸（NMSDSA）和纳米金属一硫酸钠盐（NMSMSA）这两种纳米结构的新型绿色和非均相催化剂，并通过FT-IR，能量色散X射线光谱，X射线衍射图，扫描电子显微镜，透射电子显微镜和热重分析。然后在Biginelli型反应中研究了它们的催化应用，该反应通过几种醛，乙酰乙酸乙酯和尿素或硫脲之间的一锅三组分缩合反应合成3,4-二氢嘧啶-2（1 H）-one衍生物。为了进一步研究NMSDSA和NMSMSA的催化性能，它们被用于合成聚氢喹啉和2,3-二氢喹唑啉-4（1 H）-在相同反应条件下的一种衍生物。NMSDSA和NMSMSA具有诸如成本效益，更清洁的反应曲线，良性和非均质性，催化剂的可重复使用性以及与绿色化学规程相一致的优点。所述的纳米结构催化剂具有基于天然的酸并且具有工业生产的潜力。 图形概要3,4-二氢嘧啶-2（1的合成ħ）通过的Biginelli型反应，polyhydroquinolines和2
• New chemical tools for investigating human mitotic kinesin Eg5
  作者：Emmanuel Klein、Salvatore DeBonis、Bernd Thiede、Dimitrios A. Skoufias、Frank Kozielski、Luc Lebeau

  DOI：10.1016/j.bmc.2007.06.016

  日期：2007.10

  We have designed and synthesized a series of monastrol derivatives, an allosteric inhibitor of Eg5, a motor protein responsible for the formation and maintenance of the bipolar spindle in mitotic cells. Sterically demanding structural modifications have been introduced on the skeleton of the parent drug either via a multicomponent Biginelli reaction or a stepwise modification of monastrol. The ability of these compounds to inhibit Eg5 activity has been investigated using two in vitro steady-state ATPase assays (basal and microtubule-stimulated) as well as a cell-based assay. One compound in the series appeared more potent than monastrol by a fivefold factor. Three other compounds that were unable to inhibit Eg5 ATPase activity in vitro proved potent Eg5 inhibitors in the cell-based assay. The results obtained led to the identification of structure-activity relationships further used to design an affinity matrix that can be used for fast and efficient purification of Eg5 from crude lysate of eukaryotic cells. (C) 2007 Elsevier Ltd. All rights reserved.
• 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.
• Urease Inhibitors of Agricultural Interest Inspired by Structures of Plant Phenolic Aldehydes
  作者：Lívia Horta、Yane Mota、Gisele Barbosa、Taniri Braga、Ivanildo Marriel、Ângelo de Fátima、Luzia Modolo

  DOI：10.21577/0103-5053.20160208

  日期：——

  The plant phenolic natural products (PNPs) protocatechuic aldehyde, syringaldehyde and vanillin were used as platforms for obtaining four urease inhibitors. Urea (urease substrate) or thiourea (urease inhibitor) core was added to the structure of newly synthesized compounds to provide inhibitors up to 230-fold more active than the PNPs they originated from. The PNP derivatives are mixed inhibitors with higher affinity to urease active site. Two compounds were as efficient as N-(butyl) thiophosphoric triamide (NBPT) toward soil. Overall, PNPs derivatives are promising urease inhibitors for use as additive in urea-based fertilizers formulations.
• Free radical scavenging and antiproliferative properties of Biginelli adducts
  作者：Daniel L. da Silva、Fabiano S. Reis、Dandara R. Muniz、Ana Lúcia T.G. Ruiz、João E. de Carvalho、Adão A. Sabino、Luzia V. Modolo、Ângelo de Fátima

  DOI：10.1016/j.bmc.2012.02.036

  日期：2012.4

  A series of Biginelli adducts bearing different substituents at C-4 position were synthesized by using p-sulfonic acid calix[4] arene as a catalyst. The in vitro potential to scavenge reactive nitrogen/oxygen species (RNS and ROS) and the ability to inhibit cancer cells growth were then investigated. Four adducts were found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (RNS) and/or superoxide anion (ROS) radicals. The antiproliferative activity against cancer cells was disclosed for the first time for 16 monastrol analogs. The capacity of all compounds to inhibit cancer cells growth was dependent on the histological origin of cells, except for BA24, which was highly active against all cell lines. BA20 and BA33 were as potent as the reference drug doxorubicin against adriamycin-resistant ovarian and prostate cancer cells, respectively. These results highlight some monastrol analogs as lead compounds for the design of new free radical scavengers and anticancer agents. (C) 2012 Elsevier Ltd. All rights reserved.