4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

• 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: 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid
• 英文别名: 4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylic acid
• 化学式: C₁₂H₁₂N₂O₃S
• 分子量: 264.305
• InChiKey: PEJFCUAXLCTSMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  114
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid 、 二乙二醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以87%的产率得到2-[2-[4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carbonyl]oxyethoxy]ethyl 4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate
  参考文献：
  名称：

  New chemical tools for investigating human mitotic kinesin Eg5

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2007.06.016
• 作为产物：
  描述：

  6-甲基-4-(3-羟基苯基)-2-硫代-1,2,3,4-四氢嘧啶-5-羧酸乙酯 在 水 、 potassium hydroxide 作用下， 反应 72.0h， 生成 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid
  参考文献：
  名称：

  用光开关 Eg5 抑制剂对有丝分裂进行光学控制

  摘要：

  有丝分裂驱动蛋白 Eg5 的光学控制是通过 EMD-534085 的偶氮苯类似物实现的。在紫外线条件下，HeLa 细胞发生有丝分裂停滞，单极纺锤体的形成证明了这一点。

  DOI：

  10.1002/anie.202115846

文献信息

• A novel H₂S releasing-monastrol hybrid (MADTOH) inhibits L-type calcium channels
  作者：Taniris Cafiero Braga、Itamar Couto Guedes de Jesus、Kathleen Viveiros Soares、Silvia Guatimosim、Leonardo da Silva Neto、Cristiane Jovelina da-Silva、Luzia Valentina Modolo、José Evaldo Rodrigues Menezes Filho、Paula Rhana、Jader Santos Cruz、Ângelo de Fátima

  DOI：10.1039/d0nj04415f

  日期：——

  A new alleged monastrol-H₂S releasing hybrid, named MADTOH, was designed based on the structure of monastrol (M) and 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) and synthesized in 7.8% overall yield.

  一种名为MADTOH的新型假定单纳斯特罗尔-H₂S释放杂化物被设计出来，其结构基于单纳斯特罗尔(M)和5-(4-羟基苯基)-3H-1,2-二硫代噻吩-3-硫酮(ADTOH)，并以7.8%的总产率合成。

• Hybrids of 4-hydroxy derivatives of goniothalamin and piplartine bearing a diester or a 1,2,3-triazole linker as antiproliferative agents
  作者：Thiago A. Grigolo、Carolyne B. Braga、Catia Ornelas、Dennis Russowsky、Guilherme A. Ferreira-Silva、Marisa Ionta、Ronaldo A. Pilli

  DOI：10.1016/j.bioorg.2021.105292

  日期：2021.11
• 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.
• PROCEDE DE PREPARATION DE MATERIAU D'ORIGINE VEGETALE RICHE EN ACIDES PHENOLIQUES, COMPRENANT AU MOINS UN METAL, POUR LA MISE EN OEUVRE DE REACTIONS DE SYNTHESE ORGANIQUE
  申请人：Centre National de la Recherche Scientifique

  公开号：EP3600661A1

  公开（公告）日：2020-02-05
• [EN] METHOD FOR THE PRODUCTION OF A MATERIAL OF PLANT ORIGIN THAT IS RICH IN PHENOLIC ACIDS, COMPRISING AT LEAST ONE METAL, FOR CARRYING OUT ORGANIC SYNTHESIS REACTIONS<br/>[FR] PROCEDE DE PREPARATION DE MATERIAU D'ORIGINE VEGETALE RICHE EN ACIDES PHENOLIQUES, COMPRENANT AU MOINS UN METAL, POUR LA MISE EN OEUVRE DE REACTIONS DE SYNTHESE ORGANIQUE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2018178374A1

  公开（公告）日：2018-10-04

  L'invention concerne un procédé de préparation d'un matériau d'origine végétale riche en acides phénoliques, comprenant au moins un métal, ledit procédé comprenant les étapes suivantes : a. une préparation d'un matériau d'origine végétale choisi parmi : - les plantes aquatiques; - les matériaux riches en tanins; - les matériaux riches en lignine; et l'obtention d'un matériau d'origine végétal, riche en acides phénoliques, dans lequel le rapport de l'intensité de la bande de vibration de la liaison C=O du groupe COOH et de l'intensité de chacune des bandes de vibration du cycle aromatique déterminées en FT-IR est compris entre 0,5 et 4, de préférence entre 1 et 3,5, par exemple entre 1 et 2,5; b. une mise en contact du matériau d'origine végétal obtenu à l'issue de l'étape a) avec un effluent comprenant de 0,1 à 1000 mg/L d'au moins un métal, de préférence pendant une durée comprise entre 1 heure et 2 heures, à une température de préférence comprise entre 10 et 30°C; et c. l'obtention d'un matériau d'origine végétale riche en acides phénoliques comprenant de 1 à 30 % en poids d'au moins un métal par rapport au poids total du matériau.