6-(4-chlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile | 128061-80-3

• 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-(4-chlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile
• 英文别名: 4-(4-chlorophenyl)-2-(methylthio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile；2-methylsulfanyl-6-oxo-4-p-chlorophenyl-1,6-dihydropyrimidine-5-carbonitrile；4-(4-chlorophenyl)-2-(methylsulfanyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile；4-(4-Chlorophenyl)-6-hydroxy-2-(methylsulfanyl)pyrimidine-5-carbonitrile；4-(4-chlorophenyl)-2-methylsulfanyl-6-oxo-1H-pyrimidine-5-carbonitrile
• CAS: 128061-80-3
• 化学式: C₁₂H₈ClN₃OS
• mdl: MFCD10090449
• 分子量: 277.734
• InChiKey: BCKZVLHWPRWWSO-UHFFFAOYSA-N

物化性质

• 熔点：
  277-278 °C
• 沸点：
  419.3±55.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-chlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile 在 potassium carbonate 、 三氯氧磷 作用下， 以 苯 为溶剂， 反应 13.0h， 生成 4-((6-(4-chlorophenyl)-5-cyano-2-(methylthio)pyrimidin-4-yl)amino)-N-(pyrimidin-2-yl)benzenesulfonamide
  参考文献：
  名称：

  一些新的硫代嘧啶类似物的合成，抗肿瘤和抗菌测试。

  摘要：

  一些新的4-氯-嘧啶-5-甲腈（3b-d），4-取代的氨基-嘧啶-5-甲腈（4a-g），三氧代和二氧代噻唑并[3,2-a]嘧啶的合成已经描述了-6-腈（5a-c和6a-h）。评价获得的化合物的体外抗肿瘤活性。在美国国家癌症研究所（NCI）60细胞系检测中使用了单剂量（10 µM）的测试化合物。化合物3c和4f显示出对白血病的高抑制活性，而化合物3b和4d，g显示出中等活性。另一方面，筛选所有化合物的体外抗菌和抗真菌活性。化合物3d和4b对金黄色葡萄球菌显示出显着的抗菌活性。

  DOI：

  10.1248/cpb.c12-00557
• 作为产物：
  描述：

  Potassium; 6-(4-chloro-phenyl)-5-cyano-4-oxo-1,4-dihydro-pyrimidine-2-thiolate 在 potassium carbonate 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 6-(4-chlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile
  参考文献：
  名称：

  Glycosylation of 2-Thiouracil Derivatives. A Synthetic Approach to 3-Glycosyl-2, 4-dioxypyrimidines

  摘要：

  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.

  DOI：

  10.1080/07328319708001360

文献信息

• 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。
• Reaction of Pyrimidinonethione Derivatives: Synthesis of N-Methyl-2-Hydrizinopyrimidine-4-One, Thiazolo[3,4-b] N-Methylpyrimidinone; 2-(1-Pyrazolonyl) N-Methylpyrimidine-4-one and 2-Hydrazino-N-Methyl Pyrimidine-4-One Derivatives
  作者：Abdullah A. Al-Karim Al-Shara'ey

  DOI：10.1002/jccs.200400082

  日期：2004.6

  reacted with hydrazine hydrate to give the sulfur free reaction products 3a-c. These reaction products were taken as the starting materials for the synthesis of several new heterocyclic derivatives. Reaction of 3a-c with acetic anhydride and formic acid gave pyrimido triazines 4a-c and 7a-c, respectively. Their reactions with active methylene containing reagents gave the corresponding 2-(1-pyrazonyl)-N-methyl

  6-Aryl-5-cyano-4-pyrimidinone-2-thion 衍生物 1a-c 与碘甲烷 (1:2) 反应生成相应的 2-S,N-二甲基嘧啶-4-one 衍生物 2a-c。化合物2a-c依次与水合肼反应，得到无硫反应产物3a-c。这些反应产物作为合成几种新型杂环衍生物的原料。3a-c 与乙酸酐和甲酸反应分别得到嘧啶基三嗪 4a-c 和 7a-c。它们与含活性亚甲基的试剂反应分别得到相应的 2-(1-吡唑)-N-甲基嘧啶衍生物 9a-c 和 10a-c。它们与芳香醛反应得到相应的 2-腙基嘧啶衍生物 11a-c。
• Heterocyclization of thiouracil derivative: synthesis of thiazolopyrimidines, tetrazolopyrimidines and triazolopyrimidines of potential biological activity
  作者：Essam Abdelghani、Said Aly Said、M. G. Assy、Atef M. Abdel Hamid

  DOI：10.1007/s13738-015-0656-2

  日期：2015.10

  The reaction of thioxopyrimidine derivative 1a with chloroacetic acid and p-chlorobenzaldehyde gave compound 2. Alkylation of 1b using chloroacetonitrile gave N-alkylated derivative 6 which was reacted with hydrazine hydrate to give 7. Compound 7 was cyclized with formic and nitrous acid to give 8 and 9, respectively. The reaction of 1b with phosphorous oxychloride gave chloropyrimidine derivative

  硫代嘧啶衍生物1a与氯乙酸和对氯苯甲醛的反应生成化合物2。用氯乙腈将1b烷基化，得到N-烷基化衍生物6，该衍生物与水合肼反应得到7。用甲酸和亚硝酸使化合物7环化，分别得到8和9。的反应1B与磷酰氯，得到氯衍生物10，其进行反应和环化用不同的试剂，得到化合物11 - 23。研究了针对革兰氏阳性和革兰氏阴性细菌的抗菌活性。
• Novel Pyrimidinone Derivatives: Synthesis, Antitumor and Antimicrobial Evaluation
  作者：Azza Taher Taher、Amira Atef Helwa

  DOI：10.1248/cpb.60.521

  日期：——

  Starting from 6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (4a–d), a series of mono- and dialkyl derivatives 5a–j and 6a, b was synthesized. Hydrazinolysis of 4a, b, d and 5d afforded the hydrazino derivatives 7a–c which were cyclised to give the triazolopyrimidinones 8a–c and the pyrimidotriazinones 9a–c through the reaction with formic acid and chloroacetyl chloride, respectively. Most of the newly synthesized compounds were evaluated for their in-vitro antitumor activity. Compounds 6a and b displayed promising anticancer activity against leukaemia, non-small cell lung, melanoma, and renal cancer. On the other hand, all compounds prepared were screened for their in-vitro antibacterial and antifungal activities. Compounds 5h and j showed significant activity against Staphylococcus aureus, while compounds 5e, 7c and 8c displayed moderate inhibitory activity against Candida albicans.

  以6-芳基-4-氧代-2-硫代-1,2,3,4-四氢嘧啶-5-碳腈（4a–d）为起始材料，合成了一系列单烷基和双烷基衍生物5a–j和6a，b。对4a、b、d和5d进行肼解反应，得到肼基衍生物7a–c，随后通过与甲酸和氯乙酰氯反应环化，分别得到三唑嘧啶酮8a–c和嘧啶三嗪酮9a–c。大多数新合成的化合物经过体外抗肿瘤活性评估。化合物6a和b在对白血病、非小细胞肺癌、黑色素瘤和肾癌方面表现出良好的抗癌活性。另一方面，所有合成的化合物均经过体外抗菌和抗真菌活性筛选。化合物5h和j对金黄色葡萄球菌表现出显著活性，而化合物5e、7c和8c对白色念珠菌表现出中等抑制活性。
• Design, synthesis and biological evaluation of novel morpholinopyrimidine-5-carbonitrile derivatives as dual PI3K/mTOR inhibitors
  作者：Ghada S. Rady、Moshira A. El Deeb、Marwa T. M. Sarg、Azza T. Taher、Amira A. Helwa

  DOI：10.1039/d3md00693j

  日期：——

  at position 2, with or without spacers, of the new key intermediate 2-hydrazinyl-6-morpholinopyrimidine-5-carbonitrile (5) yielded compounds 6–10, 11a–c and 12a–h. The National Cancer Institute (USA) tested all compounds for antiproliferative activity. Schiff bases, 12a–h analogs, were the most active ones. The most promising compounds 12b and 12d exhibited excellent antitumor activity against the

  在本研究中，设计并合成了新型吗啉代嘧啶-5-甲腈作为 PI3K/mTOR 双重抑制剂和凋亡诱导剂。新的关键中间体 2-肼基-6-吗啉代嘧啶-5-甲腈 ( 5 ) 在 2 位（带或不带间隔基）整合杂环，产生化合物6-10、11a -c和12a-h 。美国国家癌症研究所测试了所有化合物的抗增殖活性。席夫碱、 12a-h类似物是最活跃的碱。最有前途的化合物12b和12d对白血病 SR 细胞系（最敏感的细胞系）表现出优异的抗肿瘤活性，IC 50分别为 0.10 ± 0.01 和 0.09 ± 0.01 μM，并对 PI3Kα/PI3Kβ/PI3Kδ 具有显着影响与 LY294002 相比， 12b的 IC 50值分别为 0.17 ± 0.01、0.13 ± 0.01 和 0.76 ± 0.04 μM， 12d的 IC 50 值分别为 1.27 ± 0.07、3.20 ± 0.16 和 1.98 ±