1-(4-甲基苯基)-2,4,6(1H,3H,5H)-嘧啶三酮 | 16348-04-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1-(4-甲基苯基)-2,4,6(1H,3H,5H)-嘧啶三酮
• 英文名称: 1-(4-tolyl)pyrimidin-2,4,6(1H,3H,5H)-trione
• 英文别名: 1-p-tolylpyrimidine-2,4,6-trione；1-p-tolyl-pyrimidine-2,4,6-trione；1-p-tolyl-barbituric acid；1-p-Tolyl-barbitursaeure；1-(p-Tolyl)-barbitursaeure；1-p-Tolyl-pyrimidine-2,4,6-trione；1-(4-methylphenyl)-1,3-diazinane-2,4,6-trione
• CAS: 16348-04-2
• 化学式: C₁₁H₁₀N₂O₃
• mdl: MFCD00815752
• 分子量: 218.212
• InChiKey: WLGYFVCNEFNYKO-UHFFFAOYSA-N

物化性质

• 熔点：
  243-244 °C
• 密度：
  1.334±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933540000

反应信息

• 作为反应物：
  描述：

  1-(4-甲基苯基)-2,4,6(1H,3H,5H)-嘧啶三酮 在 吡啶 、 溴 作用下， 以 乙醇 为溶剂， 生成 (3'aR,5'R,6'R,7'S,7'aR)-6',7'-dihydroxy-5'-(hydroxymethyl)-1-(4-methylphenyl)spiro[1,3-diazinane-5,2'-5,6,7,7a-tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran]-2,4,6-trione
  参考文献：
  名称：

  Synthesis of Novel Galactopyranosyl‐Derived Spiro Barbiturates

  摘要：

  Malonic acid undergoes condensation readily with ureas to yield barbituric acids 2, which on bromination give 5,5-dibromobarbituric acids 3. Reaction of alpha-D-galactose with these 5,5-dibromo barbituric acids afforded 2,3-alpha-D-galactopyrano-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,10-triones 4. The structures of the products have been assigned on the basis of H-1 NMR, C-13 NMR, FAB-MS, optical activity, and elemental analysis. The title compounds are found to have antibacterial and antifungal activities.

  DOI：

  10.1080/07328300601039328
• 作为产物：
  描述：

  乙烷,三氯氟- 在 sodium 、 溶剂黄146 、 尿素 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 生成 1-(4-甲基苯基)-2,4,6(1H,3H,5H)-嘧啶三酮
  参考文献：
  名称：

  优化用于治疗急性早幼粒细胞白血病的有效的，选择性的，可逆的LSD1抑制剂5-亚芳基巴比妥酸盐

  摘要：

  组蛋白赖氨酸特异性脱甲基酶1（LSD1）在各种血液系统疾病中过表达，被公认为是血液药物的有希望的靶标。在这项研究中，结合生物评估的基于分子对接的虚拟筛选被用来鉴定5-芳基巴比妥酸酯的新骨架作为LSD1的小分子抑制剂。在合成的衍生物中，12a 对MAO-A和MAO-B表现出可逆和有效的抑制作用（IC 50 = 0.41μM）和高选择性。值得注意的是，12a强烈诱导了对急性早幼粒细胞白血病NB4细胞系的分化作用，并明显提高了组蛋白3赖氨酸4（H3K4）的甲基化水平。我们的研究结果表明5-芳基巴比妥酸酯可能代表了LSD1抑制剂的新骨架和12a应该作为进一步研究的有希望的媒介。

  DOI：

  10.1016/j.bmc.2018.08.026

文献信息

• A new method for the synthesis of 5-amidinobarbiturates
  作者：I. V. Paramonov、N. A. Belyaev、V. A. Bakulev

  DOI：10.1007/s11172-007-0253-3

  日期：2007.8

  The reactions of 5-[arylamino(methylthio)methylene]pyrimidine-2,4,6(1H,3H,5H)-triones with different aliphatic and aromatic amines were studied. A series of 5-amidinobarbiturates was synthesized. A new and preparatively convenient method for their synthesis appropriate for the use in the combinatorial chemistry was developed.

  研究了5-[芳基氨基(甲硫基)亚甲基]嘧啶-2,4,6(1H,3H,5H)-triones与不同脂肪族和芳香族胺的反应。合成了一系列 5-脒基巴比妥酸盐。开发了一种新的、制备方便的合成方法，适用于组合化学。
• Discovery of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 5-(aminomethylene)pyrimidine-2,4,6-trione moiety as c-Met kinase inhibitors
  作者：Qidong Tang、Guogang Zhang、Xinming Du、Wufu Zhu、Ruijuan Li、Huafang Lin、Pengcheng Li、Maosheng Cheng、Ping Gong、Yanfang Zhao

  DOI：10.1016/j.bmc.2014.01.014

  日期：2014.2

  A series of novel quinoline derivatives bearing 5-(aminomethylene)pyrimidine-2,4,6-trione moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) in vitro. Most compounds showed moderate to excellent potency, with the most promising analogue 45 (c-Met half-maximal inhibitory concentration [IC50] = 1.15 nM) showing high selectivity versus 5 other tyrosine kinases, VEGFR-2, Flt-3, PDGFR-beta, c-Kit, and EGFR. Structure-activity relationship studies indicated that electron-donating groups on the phenyl ring at the 3-position of pyrimidine-2,4,6-trione were required to increase the electron density on the 5-(aminomethylene) pyrimidine-2,4,6-trione moiety. (C) 2014 Elsevier Ltd. All rights reserved.
• Some Nitrogen Substituted Barbituric Acids and their Derivatives¹
  作者：Dorothy Nightingale、Claude H. Alexander

  DOI：10.1021/ja01296a033

  日期：1936.5
• ——
  作者：K. A. Krasnov、V. G. Kartsev、E. E. Santarovich

  DOI：10.1023/a:1019973404301

  日期：——
• Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction
  作者：Ibrahim M. El-Deeb、Said M. Bayoumi、Magda A. El-Sherbeny、Alaa A.-M. Abdel-Aziz

  DOI：10.1016/j.ejmech.2010.02.038

  日期：2010.6

  Novel derivatives of 5-(substituted)benzylidene-3-(4-substituted)phenylsulfonylimidazolidine-2,4-diones (3a-r), 1-(4-substituted)phenylsulfonyl-3-(4-substituted)phenylpyrimidine-2,4,6-(1H,3H,5H)-triones (6a-l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1H,3H)-diones (8a-l) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from 9 different organs. The tested compounds have showed good inhibitory effect at the ovarian cancer (IGROV1) cell line. A significant inhibition for (RXF393) renal cancer cells was observed with series 3 compounds, while in the other two series 6 and 8, there was a significant inhibition of ovarian cancer cells (OVCAR-8) and melanoma cells (SK-MEL-2). Interestingly, beside the strong inhibition of compound 3q to IGROV1 and RXF393 cells, a great inhibition (199 62%) for (M14) Melanoma cells was observed at the tested concentration (10 mu M) ADME-T and pharmacophore prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.