6-(2-benzylidene-1-methylhydrazino)-3-methyluracil | 32502-53-7

• 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: 6-(2-benzylidene-1-methylhydrazino)-3-methyluracil
• 英文别名: benzaldehyde N-methyl-N-(3-methyluracil-6-yl)hydrazone；6-[N-[(E)-benzylideneamino]-N-methylamino]-3-methyl-1H-pyrimidine-2,4-dione；6-[[(E)-benzylideneamino]-methyl-amino]-3-methyl-1H-pyrimidine-2,4-dione；6-[(2E)-2-benzylidene-1-methylhydrazinyl]-3-methylpyrimidine-2,4(1H,3H)-dione；6-[[(E)-benzylideneamino]-methylamino]-3-methyl-1H-pyrimidine-2,4-dione
• CAS: 32502-53-7
• 化学式: C₁₃H₁₄N₄O₂
• 分子量: 258.28
• InChiKey: GBYCYUXRPYOIKL-NTEUORMPSA-N

物化性质

• 熔点：
  245 °C(Solv: ethanol (64-17-5))
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(2-benzylidene-1-methylhydrazino)-3-methyluracil 在 溶剂黄146 、 sodium hydroxide 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 8.0h， 生成 1,5-dimethyl-3-phenyl-1H-imidazo[4,5-e][1,2,4]triazin-6(5H)-one
  参考文献：
  名称：

  新型KDM4C抑制剂的合理设计，合成和生物学分析。

  摘要：

  KDM4家族的人组蛋白脱甲基酶已经与诸如前列腺癌和乳腺癌的疾病有关。当前已知的大多数抑制剂都遭受酶同工型之间的低渗透性和低选择性。在这项研究中，毒素黄素被用于设计和合成具有改善的生物活性和体外ADME特性的新型KDM4C抑制剂。抑制剂表现出良好的被动细胞通透性和代谢稳定性。然而，减少氧化还原责任并因此对细胞生存力的非特异性影响仍然是一个挑战。

  DOI：

  10.1016/j.bmc.2019.115128
• 作为产物：
  描述：

  6-氯-3-甲基尿嘧啶 以 乙醇 为溶剂， 反应 0.34h， 生成 6-(2-benzylidene-1-methylhydrazino)-3-methyluracil
  参考文献：
  名称：

  新型KDM4C抑制剂的合理设计，合成和生物学分析。

  摘要：

  KDM4家族的人组蛋白脱甲基酶已经与诸如前列腺癌和乳腺癌的疾病有关。当前已知的大多数抑制剂都遭受酶同工型之间的低渗透性和低选择性。在这项研究中，毒素黄素被用于设计和合成具有改善的生物活性和体外ADME特性的新型KDM4C抑制剂。抑制剂表现出良好的被动细胞通透性和代谢稳定性。然而，减少氧化还原责任并因此对细胞生存力的非特异性影响仍然是一个挑战。

  DOI：

  10.1016/j.bmc.2019.115128

文献信息

• Syntheses of 1,6-dimethylpyrimido(4,5-c)pyridazine-5,7(1H, 6H)-diones (4-deazatoxoflavins) and their use in the autorecycling oxidation of alcohols and amines.
  作者：FUMIO YONEDA、KEISHI NAKAGAWA、MITSUKO NOGUCHI、MASATSUGU HIGUCHI

  DOI：10.1248/cpb.29.379

  日期：——

  Treatment of 3-methyl-6-(1-methylhydrazino) uracil (I) with phenacyl bromides in ethanol afforded the corresponding 3-aryl-4, 8-dihydro-1, 6-dimethylpyrimido [4, 5-c]-pyridazine-5, 7 (1H, 6H)-diones (3-aryl-4, 8-dihydro-4-deazatoxoflavins) (II) and 3-aryl-1, 7-dimethyl-6, 8-dioxo-1, 4, 6, 7, 8-pentahydropyrimido [4, 3-c]-as-triazines (III). Oxidation of II with diethyl azodicarboxylate gave the corresponding 3-aryl-4-deazatoxoflavins (IV) in quantitative yields. The reaction of aryl aldehyde N-methyl-N-(3-methyluracil-6-yl)-hydrazones (VII) with triethyl orthoformate in dimethylformamide also gave the corresponding 3-aryl-4-deazatoxoflavins (IV). Compounds IV thus obtained oxidized alcohols under alkaline conditions in the dark to yield the corresponding carbonyl compounds, while they themselves were hydrogenated to compounds II. Under certain conditions, these oxidations were automatically recycled to give the corresponding carbonyl compounds in more than 100% yields.

  在乙醇中将 3-甲基-6-(1-甲基肼基)尿嘧啶(I)与苯乙酰溴处理，可得到相应的 3-芳基-4，8-二氢-1，6-二甲基嘧啶并[4，5-c]哒嗪-5、7(1H，6H)-二酮（3-芳基-4，8-二氢-4-脱氮恶黄素）（II）和 3-芳基-1，7-二甲基-6，8-二氧代-1，4，6，7，8-五氢嘧啶并[4，3-c]-as-三嗪（III）。用偶氮二甲酸二乙酯对 II 进行氧化，可以定量得到相应的 3-芳基-4-脱氮恶黄素（IV）。芳基醛 N-甲基-N-（3-甲基尿嘧啶-6-基）-肼（VII）与原甲酸三乙酯在二甲基甲酰胺中的反应也得到了相应的 3-芳基-4-脱氮恶黄素（IV）。这样得到的化合物 IV 在黑暗的碱性条件下氧化醇，生成相应的羰基化合物，而它们本身则氢化成化合物 II。在某些条件下，这些氧化反应会自动循环，生成相应的羰基化合物，收率超过 100%。
• 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.
• Facile and General Syntheses of 1-Alkyltoxoflavin and 8-Alkylfervenulin Derivatives of Biological Significance by the Regiospecific Alkylation of Reumycin (1-Demethyltoxoflavin, 8-Demethylfervenulin) Derivatives
  作者：Tomohisa Nagamatsu、Hirofumi Yamasaki

  DOI：10.3987/com-97-7750

  日期：——

  Regiospecific alkylation of reumycins (6) under alkaline conditions with a dialkyl sulfate or alkyl halide in dioxane and in DMF to provide 1-alkyltoxoflavins (5) of biological significance and 8-alkylfervenulins (7), respectively, is described.
• YONEDA FUMIO; NAKAGAWA KEISHI; NOGUCHI MITSUKO; HIGUCHI MASATSUGU, CHEM. AND PHARM. BULL., 1981, 29, NO 2, 379-385
  作者：YONEDA FUMIO、 NAKAGAWA KEISHI、 NOGUCHI MITSUKO、 HIGUCHI MASATSUGU

  DOI：——

  日期：——
• YOUEDA F.; NAGAMATSU T., BULL. CHEM. SOC. JAP. <BCSJ-A8>, 1975, 48, NO 5, 1484-1489
  作者：YOUEDA F.、 NAGAMATSU T.

  DOI：——

  日期：——