6-benzylaminouracil | 5759-80-8

• 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-benzylaminouracil
• 英文别名: 6-benzylamino-1H-pyrimidine-2,4-dione；4-Benzylamino-uracil；6-(benzylamino)-1H-pyrimidine-2,4-dione
• CAS: 5759-80-8
• 化学式: C₁₁H₁₁N₃O₂
• 分子量: 217.227
• InChiKey: NORSBFZJRBPBQZ-UHFFFAOYSA-N

物化性质

• 熔点：
  308-310 °C
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  >32.6 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 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-benzylaminouracil 在 乙酸酐 、 potassium carbonate 、 溶剂黄146 、 cesium fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.33h， 生成
  参考文献：
  名称：

  Protochlorophyllide Reductase III: Synthesis of a Protochlorophyllide-Dihydroflavin Complex

  摘要：

  Abstract— A mild and efficient method of linking a dihydroflavin to the C‐17 carboxylic acid side chain of protochlorophyllide, without degradation of the sensitive E ring or loss of magnesium, is described. The appended dihydroflavin was shown to quench the fluorescence of protochlorophyllide. In contrast, a dihydronicotinamide moiety was unable to effect fluorescence quenching. The relevance of these findings to a possible mechanism of action of the enzyme protochlorophyllide reductase is discussed.

  DOI：

  10.1111/j.1751-1097.1996.tb02998.x
• 作为产物：
  描述：

  6-氯尿嘧啶 、 苄胺 反应 0.25h， 以94%的产率得到6-benzylaminouracil
  参考文献：
  名称：

  在聚焦微波辐射下氟尿嘧啶与硒，硫，氧和氮亲核试剂反应合成取代的尿嘧啶

  摘要：

  在微波辐射下，氟脲与硒，硫，氧和氮亲核试剂的亲核取代反应在几分钟内完成，收率高达99％。使用微波辐射的方法优于在常规加热过程下进行的方法。

  DOI：

  10.1016/j.tet.2005.01.085

文献信息

• Inhibitors of Bacillus subtilis DNA polymerase III. Influence of modifications in the pyrimidine ring of anilino- and (benzylamino)pyrimidines
  作者：Debra J. Trantolo、George E. Wright、Neal C. Brown

  DOI：10.1021/jm00155a016

  日期：1986.5

  examined in several series of N6-substituted 6-aminopyrimidines. The presence of alkyl groups as large as n-butyl in the 3-position of 6-(5-indanylamino)uracil had no effect on inhibitor-enzyme binding. Substituents in the 4-position of a series of 2-amino-6-(benzylamino)pyrimidines had complex effects: alkoxy and phenoxy derivatives were less active than the parent 4-oxo (isocytosine) compound, but alkylphenoxy

  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。
• 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.
• 5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2
  作者：Michael P. Dickens、Patricia Roxburgh、Andreas Hock、Mokdad Mezna、Barrie Kellam、Karen H. Vousden、Peter M. Fischer

  DOI：10.1016/j.bmc.2013.09.038

  日期：2013.11

  Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e. g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
• Annulation of 6-aminouracils with 2,3-dimethoxy- and 2-fluorobenzaldehydes and 2-chloro-7-methoxyquinoline-3-carbaldehyde
  作者：R. G. Melik-Ohanjanyan、T. R. Hovsepyan、S. G. Israelyan、G. S. Karakhanyan、N. S. Minasyan

  DOI：10.1134/s1070428015100152

  日期：2015.10

  6-R-Aminouracils reacted with 2,3-dimethoxybenzaldehyde to give 10-R-substituted 9-methoxy-5-deazaflavins. No expected 5-deazaflavins were obtained in analogous reactions of 2,3-dimethoxybenzaldehyde with 6-aminouracil hydrochlorides. On the other hand, the corresponding 5-deazaflavin and naphthyridine hydrochlorides were formed in the reactions of 6-aminouracil hydrochlorides with 2-fluorobenzaldehyde and 2-chloro-7-methoxyquinoline-3-carbaldehyde. The newly synthesized 9,10-substituted 5-deazaflavins and benzo[b]pyrimido[5,4-g][1,8]naphthyridines attract interest as potential biologically active substances and substrates for further structural modifications.
• New Synthesis and Biologically Active Molecular Design of Deazapteridine-Steroid Hybrid Compounds
  作者：Tomohisa Nagamatsu、Hiroki Yamada、Kazuyuki Shiromoto

  DOI：10.3987/com-03-9925

  日期：——

  This paper describes a facile and general synthesis of a new class of the hybrid compounds (4, 5 and 16), possessing 5-deazapteridine and steroid in the same ring system, by condensation of 6-(monosubstituted amino)uracils (9) or 6-(monosubstituted amino)-2-phenylpyrimidin-4(3H)-ones (14) with 2-hydroxymethyleneandrostanolone (10) or 2-hydroxymethylenetestosterone (15) under heating in the presence of p-toluenesulfonic acid monohydrate and their potential unti-coccidiosis activities.