N,N-diethyl-4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide

• 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: N,N-diethyl-4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
• 英文别名: N,N-diethyl-4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxamide
• 化学式: C₁₆H₂₁N₃O₂S
• 分子量: 319.428
• InChiKey: HZLZVLJJVHCLCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  96.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  间羟基苯甲醛 、 硫脲 、 N,N-二乙基乙酰乙酰胺 在 iron(III) chloride hexahydrate 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以52.75%的产率得到N,N-diethyl-4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
  参考文献：
  名称：

  一锅合成硫代四氢嘧啶衍生物作为有效的β-葡萄糖醛酸苷酶抑制剂，生物学评估，分子对接和分子动力学研究。

  摘要：

  已经合成了一系列的N，N-二乙基苯基硫代-四氢嘧啶羧酰胺，并研究了它们的β-葡萄糖醛酸苷酶抑制活性。所有分子均表现出优异的抑制作用，IC50值为0.35至42.05 µM，甚至比标准的d-蔗糖酸更有效。结构-活性关系分析表明，间-芳基取代的衍生物显着影响β-葡萄糖醛酸苷酶的抑制活性，而对位取代对应物的表现优于中等效力。该系列中最有效的化合物是带有噻吩基序的4g化合物，IC50为0.35±0.09 µM。为了验证SAR，还进行了分子对接和分子动力学研究。

  DOI：

  10.1016/j.bmc.2020.115359

文献信息

• 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.
• Synthesis of 6-aryl-N,N-diethyl-4-methyl-2-sulfanylidene-1,2,3,6-tetrahydropyrimidine-5-carboxamides
  作者：V. L. Gein、N. A. Buzmakova、T. M. Zamaraeva、M. V. Dmitriev

  DOI：10.1134/s1070428016040163

  日期：2016.4

  Three-component condensation of N,N-diethyl-3-oxobutanamide with aromatic aldehydes and thiourea afforded the corresponding 6-aryl-N,N-diethyl-4-methyl-2-sulfanylidene-1,2,3,6-tetrahydropyrimidine-5-carboxamides.
• One-pot synthesis of thioxo-tetrahydropyrimidine derivatives as potent β-glucuronidase inhibitor, biological evaluation, molecular docking and molecular dynamics studies
  作者：Aida Iraji、Ali Nouri、Najmeh Edraki、Somayeh Pirhadi、Mahsima Khoshneviszadeh、Mehdi Khoshneviszadeh

  DOI：10.1016/j.bmc.2020.115359

  日期：2020.4

  synthesized and investigated for their β-glucuronidase inhibitory activities. All molecules exhibited excellent inhibition with IC50 values ranging from 0.35 to 42.05 µM and found to be even more potent than the standard d-saccharic acid. Structure-activity relationship analysis indicated that the meta-aryl-substituted derivatives significantly influenced β-glucuronidase inhibitory activities while the para-substitution

  已经合成了一系列的N，N-二乙基苯基硫代-四氢嘧啶羧酰胺，并研究了它们的β-葡萄糖醛酸苷酶抑制活性。所有分子均表现出优异的抑制作用，IC50值为0.35至42.05 µM，甚至比标准的d-蔗糖酸更有效。结构-活性关系分析表明，间-芳基取代的衍生物显着影响β-葡萄糖醛酸苷酶的抑制活性，而对位取代对应物的表现优于中等效力。该系列中最有效的化合物是带有噻吩基序的4g化合物，IC50为0.35±0.09 µM。为了验证SAR，还进行了分子对接和分子动力学研究。