6-(4-methylphenylamino)-1H-pyrimidine-2,4-dione | 6948-11-4

• 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-methylphenylamino)-1H-pyrimidine-2,4-dione
• 英文别名: 6-(4-methyl-anilino)-1H-pyrimidine-2,4-dione；6-[(4-methylphenyl)amino]pyrimidine-2,4(1H,3H)-dione；6-(4-methylanilino)-1H-pyrimidine-2,4-dione
• CAS: 6948-11-4
• 化学式: C₁₁H₁₁N₃O₂
• 分子量: 217.227
• InChiKey: QKHUPPJBNXWLJB-UHFFFAOYSA-N

物化性质

• 熔点：
  321-323 °C(Solv: water (7732-18-5); ethyl ether (60-29-7); methanol (67-56-1))
• 密度：
  1.324±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 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-methylphenylamino)-1H-pyrimidine-2,4-dione 在 溴 作用下， 以 溶剂黄146 为溶剂， 以43%的产率得到5-bromo-6-(p-toluidino)uracil
  参考文献：
  名称：

  枯草芽孢杆菌DNA聚合酶III的抑制剂。苯胺基和（苄基氨基）嘧啶的嘧啶环中修饰的影响。

  摘要：

  在几个N6-取代的6-氨基嘧啶系列中，研究了对抑制枯草芽孢杆菌DNA聚合酶III的替代作用。在6-（5-茚满基氨基）尿嘧啶的3-位上存在与正丁基一样大的烷基对抑制剂-酶结合没有影响。一系列2-氨基-6-（苄氨基）嘧啶的4-位取代基具有复杂的作用：烷氧基和苯氧基衍生物的活性低于母体4-氧代（异胞嘧啶）化合物，而烷基苯氧基和卤代苯氧基衍生物的活性更高与4-苯氧基化合物本身相比，这表明在4-取代基和酶表面之间可以发生疏水结合，并且嘧啶环和pol III之间的空间可能代表了酶的活性位点。用甲基和乙基取代5-H大大降低了6-（苄氨基）-和6-对甲苯基尿嘧啶的抑制活性，但5-溴和5-碘类似物与母体化合物等价。这些结果表明，这些化合物的苯环必须以与嘧啶环平面垂直的构象存在，并且这种“活性构象”的电荷转移稳定性可能会补偿抑制剂中5个卤代基的空间位阻，酶复合物。

  DOI：

  10.1021/jm00155a016
• 作为产物：
  描述：

  6-氯尿嘧啶 、 乙烷,三氯氟- 反应 0.33h， 以91%的产率得到6-(4-methylphenylamino)-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

• Photocatalytic Oxidative [2+2] Cycloelimination Reactions with Flavinium Salts: Mechanistic Study and Influence of the Catalyst Structure
  作者：Tomáš Hartman、Martina Reisnerová、Josef Chudoba、Eva Svobodová、Nataliya Archipowa、Roger Jan Kutta、Radek Cibulka

  DOI：10.1002/cplu.202000767

  日期：2021.3

  and investigated their application in light‐dependent oxidative cycloelimination of cyclobutanes. Detailed mechanistic investigations with a coumarin dimer as a model substrate reveal that the reaction preferentially occurs via the triplet‐born radical pair after electron transfer from the substrate to the triplet state of an alloxazinium salt. The very photostable 7,8‐dimethoxy derivative is a superior

  黄鎓盐经常用于有机催化，但迄今为止尚未系统地研究它们在光氧化还原催化中的应用。我们合成了一系列在 7 位和 8 位具有不同取代基的 5-乙基-1,3-二甲基恶嗪盐，并研究了它们在环丁烷的光依赖氧化环消除中的应用。以香豆素二聚体作为模型底物的详细机理研究表明，在电子从底物转移到咯嗪盐的三重态后，反应优先通过三重态自由基对发生。非常光稳定的 7,8-二甲氧基衍生物是一种优异的催化剂，具有足够高的氧化能力 ( E * = 2.26 V)，允许转化各种环丁烷（具有E ox高达 2.05 V) 的高产率。甚至诸如全反式二甲基 3,4-双(4-甲氧基苯基)环丁烷-1,2-二羧酸酯之类的化合物也可以转化，由于顺式中庞大的相邻取代基导致缺少预活化，因此其打开需要高活化能-位置。
• 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。
• Compounds inhibiting the aggregation of superoxide dismutase-1
  申请人：Lansbury Peter

  公开号：US20060194821A1

  公开（公告）日：2006-08-31

  The invention is directed to methods of inhibiting the rate at which superoxide dismutse-1 (SOD) aggregates using compounds that stabilize SOD dimers. The methods are useful in the study and therapy of amyotrophic lateral sclerosis. The invention also includes assays that can be used to identify compounds that stabilize dimers and SOD molecules that have been modified for use in these assays.

  本发明涉及使用稳定SOD二聚体的化合物来抑制超氧化物歧化酶-1（SOD）聚集的速率的方法。该方法在进行肌萎缩侧索硬化的研究和治疗中非常有用。本发明还包括可用于识别稳定二聚体化合物和已经改性用于这些测定的SOD分子的测定方法。
• 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.
• 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.