1-(4-chlorophenyl)pyrimidine-2,4,6(1H,3H,5H)-trione | 90767-54-7

• 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: 1-(4-chlorophenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
• 英文别名: 1-(4-chlorophenyl)pyrimidine-2,4,6-trione；1-(4-chlorophenyl)barbituric acid；1-(4-chlorophenyl)-1,3-diazinane-2,4,6-trione
• CAS: 90767-54-7
• 化学式: C₁₀H₇ClN₂O₃
• mdl: MFCD00447898
• 分子量: 238.63
• InChiKey: BJHJQYAOKVCTBQ-UHFFFAOYSA-N

物化性质

• 熔点：
  180 °C(Solv: ethanol (64-17-5))
• 密度：
  1.499±0.06 g/cm3(Predicted)
• 溶解度：
  >35.8 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 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-chlorophenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 在 苄基三乙基氯化铵 、 三氯氧磷 作用下， 反应 6.0h， 以85%的产率得到6-chloro-3-(4-chlorophenyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide

  摘要：

  Topoisomerase II (TOP2) poisons as anticancer drugs work by trapping TOP2 cleavage complexes (TOP2cc) to generate DNA damage. Repair of such damage by tyrosyl DNA phosphodiesterase 2 (TDP2) could render cancer cells resistant to TOP2 poisons. Inhibiting TDP2, thus, represents an attractive mechanism-based chemosensitization approach. Currently known TDP2 inhibitors lack cellular potency and/or permeability. We report herein two novel subtypes of the deazaflavin TDP2 inhibitor core. By introducing an additional phenyl ring to the N-10 phenyl ring (subtype 11) or to the N-3 site of the deazaflavin scaffold (subtype 12), we have generated novel analogues with considerably improved biochemical potency and/or permeability. Importantly, many analogues of both subtypes, particularly compounds 11a, 11e, 12a, 12b, and 12h, exhibited much stronger cancer cell sensitizing effect than the best previous analogue 4a toward the treatment with etoposide, suggesting that these analogues could serve as effective cellular probes.

  DOI：

  10.1021/acs.jmedchem.9b00274
• 作为产物：
  描述：

  丙二酸二乙酯 、 4-氯苯基脲 在 乙醇 、 sodium 作用下， 反应 5.0h， 以51%的产率得到1-(4-chlorophenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  Cyplecksin是细胞粘附素的Pleckstrin同源域的共价抑制剂

  摘要：

  共价结合：一类新的5-溴巴比妥酸盐（Cyplecksins;参见结构）通过共价机制起作用，抑制细胞粘附素的pleckstrin同源域的生物学功能，这是Ras样ARF-GTPase的小鸟嘌呤核苷酸交换因子。在细胞中，Cyplecksins会干扰依赖磷酸肌醇的细胞粘附素膜募集。胱抑素可用于验证细胞粘附素作为潜在的药物靶标。

  DOI：

  10.1002/anie.201302207

文献信息

• Cyplecksins Are Covalent Inhibitors of the Pleckstrin Homology Domain of Cytohesin
  作者：Mohamed Hussein、Martina Bettio、Anton Schmitz、Jeffrey S. Hannam、Julian Theis、Günter Mayer、Stefan Dosa、Michael Gütschow、Michael Famulok

  DOI：10.1002/anie.201302207

  日期：2013.9.2

  The covalent grip: A new class of 5‐bromobarbiturates (Cyplecksins; see structure) act by a covalent mechanism to inhibit the biological function of the pleckstrin homology domain of cytohesins, small guanine nucleotide exchange factors for the Ras‐like ARF‐GTPases. In cells, Cyplecksins interfere with the phosphoinositol‐dependent membrane recruitment of cytohesins. Cyplecksins may be useful in validating

  共价结合：一类新的5-溴巴比妥酸盐（Cyplecksins;参见结构）通过共价机制起作用，抑制细胞粘附素的pleckstrin同源域的生物学功能，这是Ras样ARF-GTPase的小鸟嘌呤核苷酸交换因子。在细胞中，Cyplecksins会干扰依赖磷酸肌醇的细胞粘附素膜募集。胱抑素可用于验证细胞粘附素作为潜在的药物靶标。
• ——
  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.
• ——
  作者：K. A. Krasnov、V. G. Kartsev、M. N. Yurova

  DOI：10.1023/a:1014821016904

  日期：——

  The reaction of barbituric acid and its N-substituted derivatives and 2-thio analogs with cotarnine forms 5-(4-methoxy-6-methyl-5,6,7,8-tetrahildro-2H-1,3-methylenedioxy-[4,5-g]isoquinolinyl-1)barbituric acids, a new class of zwitter-ions, the structure of which was studied by H-1 and C-13 NMR spectroscopy and mass spectrometry. The prepared compounds exist in solution as stable intermolecular associates and have a complicated H-bonded structure.
• Synthesis, structural characterization and in vitro antitumor activity of 4-dimethylaminopyridinium (6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanides
  作者：Zdzislaw Brzozowski、Franciszek Sączewski、Maria Gdaniec

  DOI：10.1016/j.ejmech.2003.09.007

  日期：2003.11

  Previously, We have described a novel series of low molecular weight cancer-specific antitumor agents with aminium N-(1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamidate structure. In an attempt to determine some of the structural features that account for the cytotoxic activity of such aminium salts, a novel series of 4-dimethylaminopyridinium (1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanides (6-19) has been synthesized by the reactions of 3-methylthio-1,4,2-benzodithiazine1,1-dioxides with 4-DMAP and some active methylene compounds. The in vitro antitumor activity of these compounds has been tested in the National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed. Among the aminium salts 4-dimethylamino-pyridinium 4-chlorobenzoyl cyano (6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanide (9) was superior to other pyridinium salts in terms of both remarkable activity (log GI(50) and log TGI < -8.00) and high selectivity for the lung HOP-92 and melanoma UACC-257 cell lines. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.