6-氯-3-甲基-1-苯基-1H-嘧啶- 2,4-二酮 | 53680-90-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-氯-3-甲基-1-苯基-1H-嘧啶- 2,4-二酮
• 中文别名: 6-氯-3-甲基-1-苯基-1H-嘧啶-2,4-二酮
• 英文名称: 6-chloro-3-methyl-1-phenylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-chloro-3-methyl-1-phenyluracil；6-chloro-3-methyl-1-phenyl-1H-pyrimidine-2,4-dione；6-chloro-3-methyl-1-phenylpyrimidine-2,4-dione
• CAS: 53680-90-3
• 化学式: C₁₁H₉ClN₂O₂
• 分子量: 236.658
• InChiKey: DKGXIVRSAKPDHF-UHFFFAOYSA-N

物化性质

• 沸点：
  329.6±52.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-氯-3-甲基-1-苯基-1H-嘧啶- 2,4-二酮 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 生成 5-amino-3-methyl-6-methylamino-1-phenyluracil
  参考文献：
  名称：

  CX-659S及其相关化合物对迟发型超敏反应的抑制作用及其合成与生物学评价。

  摘要：

  为了找到对延迟型超敏反应（DTH）反应具有抑制活性的新型非甾体化合物，我们使用氯化吡啶（PC）诱导的小鼠接触超敏反应（CHR）在小鼠中进行了随机筛选，发现化合物1为铅复合。然后，我们合成并评估了一系列广泛的针对尿嘧啶和抗氧化部分的5-羧酰胺基尿嘧啶衍生物。其中，我们发现受阻酚部分对于展示其活性是必要的。特别地，发现具有维生素E的部分结构的化合物28a-28c通过口服和局部给药都具有针对DTH反应的有效活性。化合物28c对脂质过氧化具有抗氧化活性，IC50为5.9 microM。

  DOI：

  10.1016/s0968-0896(00)00126-7
• 作为产物：
  描述：

  N-甲-N’-苯脲 在 盐酸 、 sodium hydroxide 、 乙酸酐 、 三氯氧磷 作用下， 以 溶剂黄146 为溶剂， 生成 6-氯-3-甲基-1-苯基-1H-嘧啶- 2,4-二酮
  参考文献：
  名称：

  CX-659S及其相关化合物对迟发型超敏反应的抑制作用及其合成与生物学评价。

  摘要：

  为了找到对延迟型超敏反应（DTH）反应具有抑制活性的新型非甾体化合物，我们使用氯化吡啶（PC）诱导的小鼠接触超敏反应（CHR）在小鼠中进行了随机筛选，发现化合物1为铅复合。然后，我们合成并评估了一系列广泛的针对尿嘧啶和抗氧化部分的5-羧酰胺基尿嘧啶衍生物。其中，我们发现受阻酚部分对于展示其活性是必要的。特别地，发现具有维生素E的部分结构的化合物28a-28c通过口服和局部给药都具有针对DTH反应的有效活性。化合物28c对脂质过氧化具有抗氧化活性，IC50为5.9 microM。

  DOI：

  10.1016/s0968-0896(00)00126-7

文献信息

• Synthesis of Pyrimidine Derivatives Possessing an Antioxidative Property and Their Inhibitory Effects on Picryl Chloride-Induced Contact Hypersensitivity Reaction
  作者：Yoshiaki Isobe、Kosaku Hirota

  DOI：10.1248/cpb.51.1451

  日期：——

  We conducted a preliminary structure–activity relationship (SAR) study of some barbituric acid and uracil derivatives against the picryl chloride-induced contact hypersensitivity reaction. The introduction of an antioxidative moiety to the side chain of the C(6)-position of uracil was effective against this model. The introduction of dimethoxyphenol (8b) or dimethylphenol (8c) instead of di-t-butylphenol (8a) as an antioxidative moiety gave diminished activities, so, the reactive oxygen would contribute to the inflammation of this model, and an antioxidative activity was required for exhibiting the inhibitory activity. The inhibitory activity was significantly affected by the substituent at the N(1)-phenyl moiety.

  我们对一些巴比妥酸和尿嘧啶衍生物针对苦基氯引起的接触超敏反应进行了初步构效关系（SAR）研究。在尿嘧啶的 C(6) 位侧链上引入抗氧化部分可有效对抗该模型。引入二甲氧基苯酚（8b）或二甲基苯酚（8c）代替二叔丁基苯酚（8a）作为抗氧化部分会降低活性，因此，活性氧会导致该模型的炎症，因此需要抗氧化活性用于表现出抑制活性。 N(1)-苯基部分的取代基显着影响抑制活性。
• Pyrimidines. part LIIX. The Dimroth Rearrangement of 6-Aminouracil Derivatives.
  作者：Kosaku HIROTA、Pei-Zhou NI、Akiyuki SUZUKI、Hideki TAKASU、Yukio KITADE、Yoshifumi MAKI

  DOI：10.1248/cpb.40.2839

  日期：——

  The reaction of 6-amino-5-formyl (or acetyl) uracils (4) possessing a phenyl group at the 1-position with caustic alkali resulted in Dimroth rearrangement to give 6-anilino-5-formyl (or acetyl) uracils (5). This is the first example of Dimroth rearrangement observed in the uracil ring system. The presence of both the N1-phenyl group and the 5-formyl (or acetyl) group on the uracil ring is requisite for the occurrence of the rearrangement.

  6-氨基-5-甲酰基（或乙酰基）尿嘧啶（4）在1位上带有苯基，与苛性碱反应，发生迪姆罗特重排，生成6-苯胺基-5-甲酰基（或乙酰基）尿嘧啶（5）。这是迪姆罗特重排首次在尿嘧啶环系中观察到的实例。尿嘧啶环上同时存在N1-苯基和5-甲酰基（或乙酰基）基团是发生重排的必要条件。
• 1-arylpyrimidine derivatives and pharmaceutical use thereof
  申请人：Japan Energy Corporation

  公开号：US05661153A1

  公开（公告）日：1997-08-26

  The present invention relates to 1-arylpyrimidine derivatives represented by general formula (I): ##STR1## wherein R.sub.1 is H, alkyl or aralkyl; Ar is 1-naphthyl, or a substituted or unsubstituted phenyl group; R.sub.4 is a substituted phenyl, a substituted styryl, 1-methylcyclohexyl, 4-methylcyclohexyl, 4-oxo-4H-pyran-2-yl or 2-oxo-2H-pyran-5-yl group; R.sub.5 and R.sub.6 are each independently H or alkyl; R.sub.3 is H, and R.sub.7 and R.sub.8 are combined together to be oxo, or else R.sub.3 and R.sub.7 are combined together to be another direct bond, and R.sub.5 and R.sub.8 are combined together to be a direct bond, or pharmaceutically acceptable salts thereof; and methods for treating allergic diseases with such compounds.

  本发明涉及通式(I)所表示的1-芳基嘧啶衍生物：##STR1## 其中，R.sub.1是氢、烷基或芳基烷基；Ar是1-萘基，或取代或未取代的苯基；R.sub.4是取代的苯基，取代的苯乙烯基，1-甲基环己烷基，4-甲基环己烷基，4-氧代-4H-吡喃-2-基或2-氧代-2H-吡喃-5-基；R.sub.5和R.sub.6各自独立地为氢或烷基；R.sub.3是氢，R.sub.7和R.sub.8结合在一起是氧代，否则R.sub.3和R.sub.7结合在一起是另一个直接键，R.sub.5和R.sub.8结合在一起是一个直接键，或其药学上可接受的盐；以及使用这些化合物治疗过敏性疾病的方法。
• 1-Arylpyrimidine derivatives and pharmaceutical use thereof
  申请人：JAPAN ENERGY CORPORATION

  公开号：EP0700908A1

  公开（公告）日：1996-03-13

  The present invention relates to pyrimidine derivatives of the formula (I): wherein    R₁ is H, alkyl or aralkyl;    Ar is 1-naphthyl, or a substituted or unsubstituted phenyl group;    R₄ is a substituted phenyl, a substituted styryl, 1-methylcyclohexyl, 4-methylcyclohexyl, 4-oxo-4H-pyran-2-yl or 2-oxo-2H-pyran-5-yl group;    R₅ and R₆ are each independently H or alkyl;    R₃ is H, and R₇ and R₈ are combined together to be oxo, or else R₃ and R₇ are combined together to be another direct bond, and R₅ and R₈ ar combined together to be a direct bond, or pharmaceutically acceptable salts thereof; and the use of such compounds in the treatment of an allergic disease.

  本发明涉及式（I）的嘧啶衍生物： 其中 R₁ 是 H、烷基或芳烷基； Ar 是 1-萘基或取代或未取代的苯基； R₄ 是取代的苯基、取代的苯乙烯基、1-甲基环己基、4-甲基环己基、4-氧代-4H-吡喃-2-基或 2-氧代-2H-吡喃-5-基； R₅ 和 R₆ 各自独立地为 H 或烷基； R₃为H，且R₇和R₈结合在一起为氧代，或者R₃和R₇结合在一起为另一个直接键，且R₅和R₈结合在一起为一个直接键，或其药学上可接受的盐；以及此类化合物在治疗过敏性疾病中的用途。
• Investigation of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7-diones as small molecule antagonists of β-catenin/TCF transcription
  作者：Jörg Zeller、Anjanette J. Turbiak、Ian A. Powelson、Surin Lee、Duxin Sun、H.D. Hollis Showalter、Eric R. Fearon

  DOI：10.1016/j.bmcl.2013.08.111

  日期：2013.11

  Nearly all colorectal cancers (CRCs) and varied subsets of other cancers have somatic mutations leading to beta-catenin stabilization and increased beta-catenin/TCF transcriptional activity. Inhibition of stabilized beta-catenin in CRC cell lines arrests their growth and highlights the potential of this mechanism for novel cancer therapeutics. We have pursued efforts to develop small molecules that inhibit beta-catenin/TCF transcriptional activity. We used xanthothricin, a known beta-catenin/TCF antagonist of microbial origin, as a lead compound to synthesize related analogues with drug-like features such as low molecular weight and good metabolic stability. We studied a panel of six candidate Wnt/beta-catenin/Tcf-regulated genes and found that two of them (Axin2, Lgr5) were reproducibly activated (9-10 fold) in rat intestinal epithelial cells (IEC-6) following beta-catenin stabilization by Wnt-3a ligand treatment. Two previously reported beta-catenin/TCF antagonists (calphostin C, xanthothricin) and XAV939 (tankyrase antagonist) inhibited Wnt-activated genes in a dose-dependent fashion. We found that four of our compounds also potently inhibited Wnt-mediated activation in the panel of target genes. We investigated the mechanism of action for one of these (8c) and demonstrated these novel small molecules inhibit beta-catenin transcriptional activity by degrading beta-catenin via a proteasome-dependent, but GSK3 beta-, APC-, AXIN2- and beta TrCP-independent, pathway. The data indicate the compounds act at the level of beta-catenin to inhibit Wnt/beta-catenin/TCF function and highlight a robust strategy for assessing the activity of beta-catenin/TCF antagonists. (c) 2013 Elsevier Ltd. All rights reserved.