2-methylthio-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile | 97693-22-6

• 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: 2-methylthio-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile
• 英文别名: 4-Hydroxy-6-(4-methoxyphenyl)-2-(methylsulfanyl)-5-pyrimidinecarbonitrile；4-(4-methoxyphenyl)-2-methylsulfanyl-6-oxo-1H-pyrimidine-5-carbonitrile
• CAS: 97693-22-6
• 化学式: C₁₃H₁₁N₃O₂S
• 分子量: 273.315
• InChiKey: KMDPRYSSYDGWJW-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C(Solv: ethanol (64-17-5))
• 沸点：
  429.2±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 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：
  99.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methylthio-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Vasoactive Thiomethyl-Pyrimidines: Promising Drug Candidates with Vascular Activity

  摘要：

  Pyrimidines and their derivatives are present in various biologically active molecules. Most of the synthetic methods employed to achieve the pyrimidinone ring consist of two stages: the synthesis of a Michael intermediate from an aldehyde and an "active methylene" containing compound; and the condensation of this intermediate with a molecule containing an uranium moiety. This may take one to two days of laboratory work. In this paper we describe a new methodology in which these derivatives are obtained via multicomponent synthesis mediated by ultrasound in only 2 hours. In order to obtain water-soluble pyrimidinone derivatives, our previous compounds were further converted into their sodium salts. In pharmacologic studies, these salts inhibited phenylephr-ineinduced contraction in isolated rat aorta, suggesting that they may act as alpha-1 antagonists and, therefore, are candidates for anti-hypertensive drugs.

  DOI：

  10.21577/0103-5053.20160289
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 20.0h， 生成 2-methylthio-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile
  参考文献：
  名称：

  新型取代嘧啶糖苷的合成及抗病毒活性

  摘要：

  通过使嘧啶碱基与乙酰溴糖偶联反应，然后脱保护，可以合成许多N取代的嘧啶糖苷。测试合成的化合物对乙型肝炎病毒（HBV）的抗病毒活性。噬斑减少感染性测定法被用来确定由于受测试的化合物显示出中等至高的抗病毒活性而减少的病毒计数。J.杂环化​​学。（2011）。

  DOI：

  10.1002/jhet.686

文献信息

• Synthesis and Anti-HBV Activity of Novel Substituted Pyrimidine Glycosides and Their Acyclic Analogues
  作者：M. A. Hawata、W. A. El-Sayed、Adel A.-H. Abdel-Rahman

  DOI：10.1134/s1070363218080285

  日期：2018.8

  New aryl substituted uracil and thiouracil glycosides are synthesized by glycosylation at N1 in the pyrimidine nucleus using glycopyranosyl halides in basic medium. In addition C-linked hydrazinyl acyclic sugar derivatives exhibiting different sugar moieties, attached at C6, are also prepared. Antiviral activity of the newly synthesized compounds is studied against Hepatitis B virus (HBV). The antiviral

  新的芳基取代的尿嘧啶和硫尿嘧啶糖苷是通过在嘧啶核苷中的N 1处在碱性介质中使用吡喃葡萄糖基卤化物进行糖基化合成的。此外，还制备了在C 6处连接的具有不同糖部分的C-连接的肼基无环糖衍生物。研究了新合成化合物对乙型肝炎病毒（HBV）的抗病毒活性。抗病毒测试数据表明化合物6b，6c和12a-12c具有较高的活性，并具有轻微的细胞毒性作用。讨论了除芳基片段上的取代外，与取代的嘧啶系统相连的糖基部分对活性的影响。
• An efficient and facile synthesis of inhibitors for hepatitis C viral and anti-SARS agents: 4-aryl-5-cyano-1,6-dihydro-2-thiouracils
  作者：Liangce Rong、Shan Yin、Sheng Xia、Shimin Tao、Yanhui Shi、Shujiang Tu

  DOI：10.1007/s11164-011-0434-4

  日期：2012.3

  One-pot, multicomponent reaction for the synthesis of 4-aryl-5-cyano-1,6-dihydro-2-thiouracils via three-component from aromatic aldehydes, ethyl 2-cyanoacetate and S-benzylisothiourea hydrochloride (methyl carbamimidothioate sulfate) under methanol is described. These compounds have many drug activities, such as anti-hepatitis C viral, anti-Severe acute respiratory syndrome and anti-HIV-1 integrese activity. The advantages of this procedure include the short reaction time, mild reaction conditions and excellent yields.

  描述了一种一锅法多组分反应，通过芳香醛、乙基2-氰基乙酸酯和盐酸硫代脲苄基（甲基氨基硫酸酯）在甲醇中合成4-芳基-5-氰基-1,6-二氢-2-硫脲嘧啶的三组分反应。这些化合物具有多种药物活性，如抗丙型肝炎病毒、抗严重急性呼吸综合症和抗HIV-1整合酶活性。这种方法的优点包括反应时间短、反应条件温和和产率优秀。
• Synthesis and antiviral activity of new substituted pyrimidine glycosides
  作者：Mahmoud M. M. Ramiz、Wael A. El-Sayed、Ezzat Hagag、Adel A.-H. Abdel-Rahman

  DOI：10.1002/jhet.686

  日期：2011.9

  A number of N‐substituted pyrimidine glycosides were synthesized by coupling reaction of the pyrimidine base with acetobromosugars followed by deprotection. The synthesized compounds were tested for their antiviral activity against Hepatitis B Virus (HBV). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds which showed moderate

  通过使嘧啶碱基与乙酰溴糖偶联反应，然后脱保护，可以合成许多N取代的嘧啶糖苷。测试合成的化合物对乙型肝炎病毒（HBV）的抗病毒活性。噬斑减少感染性测定法被用来确定由于受测试的化合物显示出中等至高的抗病毒活性而减少的病毒计数。J.杂环化​​学。（2011）。
• Novel antiproliferative agents bearing morpholinopyrimidine scaffold as PI3K inhibitors and apoptosis inducers; design, synthesis and molecular docking
  作者：Amira A. Helwa、Nehad M. El-Dydamony、Rasha A. Radwan、Sahar M. Abdelraouf、Rana M. Abdelnaby

  DOI：10.1016/j.bioorg.2020.104051

  日期：2020.9

  active compounds 6e, 6g, and 6l against the most sensitive cell line leukemia SR were estimated (IC50 = 0.76, 13.59, and 4.37 uM, respectively). To investigate their PI3K enzyme inhibition activity, the assay was done on Class IA (α, β, & δ) isoforms. The IC50 values were very promising: compound [6e = 11.73 (α), 6.09 (β), 11.18 (δ)], compound [6g = 8.43 (α), 15.84 (β), 30.62 (δ)], and compound [6l = 13

  合成了两个新的吗啉代嘧啶衍生物系列，并由美国国家癌症研究所筛选了它们对60种肿瘤细胞系的体外细胞毒性活性。在体外的细胞毒性IC 50为最活跃的化合物的值6e中，6克和6升估计针对最敏感的细胞系白血病SR（IC 50  = 0.76，13.59和4.37微米，分别地）。为了研究其PI3K酶抑制活性，对IA类（α，β和δ）同工型进行了测定。IC 50值非常有前途：化合物[ 6e  =  11.73（α），6.09（β），与化合物相比，化合物11.6（δ）]，化合物[ 6g  =  8.43（α），15.84（β），30.62（δ）]和化合物[ 6l  =  13.98（α），7.22（β），10.94（δ）]。参考化合物LY294002 =  6.28（α），4.51（β），4.60（δ）uM。此外，对白血病SR进行细胞周期分析和膜联蛋白V-FITC染色，在G2 / M期停滞并诱导凋亡。最后，
• Glycosylation of 2-Thiouracil Derivatives. A Synthetic Approach to 3-Glycosyl-2, 4-dioxypyrimidines
  作者：A. I. Khodair、E. E. Ibrahim、E. S. H. El Ashry

  DOI：10.1080/07328319708001360

  日期：1997.4

  Reaction of 6-aryl-5-cyano-2-thiouracils 2a-d with glycosyl halides 4a,b under alkaline conditions gave the respective bisglycosylated derivatives 5a-h. However, their deacetylation with ammonia in methanol caused a cleavage of the S-glycosyl residue and gave the N-3 glycosylated analogues 6a-h.