6-(4-bromophenylamino)-1H-pyrimidine-2,4-dione | 21333-03-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(4-bromophenylamino)-1H-pyrimidine-2,4-dione
• 英文别名: 6-(4-bromoanilino)-1H-pyrimidine-2,4-dione；6-(4-Brom-phenylamino)-uracil
• CAS: 21333-03-9
• 化学式: C₁₀H₈BrN₃O₂
• 分子量: 282.096
• InChiKey: KVJLEUZMCGNFGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-bromophenylamino)-1H-pyrimidine-2,4-dione 、 4-氰基-2-氟苯甲醛 以 N,N-二甲基甲酰胺 为溶剂， 以23%的产率得到10-(4-bromophenyl)-2,4-dioxopyrimido[4,5-b]quinoline-8-carbonitrile
  参考文献：
  名称：

  Toxoflavins and Deazaflavins as the First Reported Selective Small Molecule Inhibitors of Tyrosyl-DNA Phosphodiesterase II

  摘要：

  The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAP.) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.

  DOI：

  10.1021/jm400568p
• 作为产物：
  描述：

  6-氯尿嘧啶 、 4-溴苯胺 反应 0.33h， 以80%的产率得到6-(4-bromophenylamino)-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells

  摘要：

  A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.011

文献信息

• UV₃₆₅ light promoted catalyst-free synthesis of pyrimido[4,5-<i>b</i>]quinoline-2,4-diones in aqueous-glycerol medium
  作者：Geetmani Singh Nongthombam、George Kupar Kharmawlong、John Elisa Kumar、Rishanlang Nongkhlaw

  DOI：10.1039/c8nj01459k

  日期：——

  Herein, a highly efficient and environmentally benign protocol for the synthesis of biologically important pyrimido[4,5-b]quinolinone-2,4-diones from aromatic amines, barbituric acid and aryl aldehyde is reported. This process takes place at room temperature under direct irradiation from a UV365 light source in the absence of a photocatalyst. The reported approach has several advantages such as high

  在此，报道了一种由芳族胺，巴比妥酸和芳基醛合成生物上重要的嘧啶并[4,5 - b ]喹啉酮-2,4-二酮的高效，环保的方法。该过程在室温下在不存在光催化剂的情况下在来自UV 365光源的直接照射下进行。报道的方法具有许多优势，例如高收率，干净的反应条件，无色谱法合成以及使用便宜的水-甘油溶剂系统，它也是一种环境友好的溶剂。该协议适用于大规模合成嘧啶并[4,5 - b ]喹啉酮-2,4-二酮而不浪费任何昂贵的化学药品是一个附加的优势。
• Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells
  作者：Jennifer M. Wilson、Graham Henderson、Fiona Black、Andrew Sutherland、Robert L. Ludwig、Karen H. Vousden、David J. Robins

  DOI：10.1016/j.bmc.2006.10.011

  日期：2007.1.1

  A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity. (c) 2006 Elsevier Ltd. All rights reserved.
• Toxoflavins and Deazaflavins as the First Reported Selective Small Molecule Inhibitors of Tyrosyl-DNA Phosphodiesterase II
  作者：Ali Raoof、Paul Depledge、Niall M. Hamilton、Nicola S. Hamilton、James R. Hitchin、Gemma V. Hopkins、Allan M. Jordan、Laura A. Maguire、Alison E. McGonagle、Daniel P. Mould、Mathew Rushbrooke、Helen F. Small、Kate M. Smith、Graeme J. Thomson、Fabrice Turlais、Ian D. Waddell、Bohdan Waszkowycz、Amanda J. Watson、Donald J. Ogilvie

  DOI：10.1021/jm400568p

  日期：2013.8.22

  The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAP.) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.