6-(1H-indol-3-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile | 124348-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-(1H-indol-3-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile
• 英文别名: 6-(1H-indol-3-yl)-4-oxo-2-sulfanylidene-1H-pyrimidine-5-carbonitrile
• CAS: 124348-28-3
• 化学式: C₁₃H₈N₄OS
• 分子量: 268.299
• InChiKey: CQNUSZOZYPAWDL-UHFFFAOYSA-N

物化性质

• 熔点：
  300 °C
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(1H-indol-3-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 在 五氯化磷 、 一水合肼 、 potassium hydroxide 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 13.33h， 生成 7-(1H-indol-3-yl)-3,5-dithioxo-2,3,5,6-tetrahydro[1,2,4]triazolo[4,3-c]pyrimidine-8-carbonitrile
  参考文献：
  名称：

  Novel indolyl-pyrimidine derivatives: synthesis, antimicrobial, and antioxidant evaluations

  摘要：

  In the present study, a novel series of indolyl-pyrimidines (1-13) were synthesized starting from 4-hydrazinopyrimidine-5-carbonitrile 3. Elemental analysis, IR, H-1-NMR, C-13-NMR, and mass spectral data elucidated structure of newly synthesized compounds. All compounds were screened for their in vitro antibacterial, antifungal, and some for antioxidant activities. Compounds 5, 9g, 9i, and 9j showed pronounced antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli, Candida albicans, and Aspergillus flavus compared to the reference drugs, while compounds 3 and 9g displayed promising free radical scavenging activity and found to be more potent than standard, ascorbic acid (vitamin C). Further, some compounds were evaluated for cytotoxic activity by SRB assay method against human colon carcinoma (CaCo-2) and showed that compounds 4 and 9g were found to be the highly active compared to the reference drug doxorubicin. Their structure and activity relationship were discussed.

  DOI：

  10.1007/s00044-014-0916-1
• 作为产物：
  描述：

  在 水 作用下， 反应 0.17h， 生成 6-(1H-indol-3-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile
  参考文献：
  名称：

  [EN] 2-THIOPYRIMIDINONES AS THERAPEUTIC AGENTS
  [FR] 2-THIOPYRIMIDINONES UTILISES EN TANT QU'AGENTS THERAPEUTIQUES

  摘要：

  公开号：

  WO2006031806A3

文献信息

• Potent 5-Cyano-6-phenyl-pyrimidin-Based Derivatives Targeting DCN1–UBE2M Interaction
  作者：Wenjuan Zhou、Liying Ma、Lina Ding、Qian Guo、Zhangxu He、Jing Yang、Hui Qiao、Lingyu Li、Jie Yang、Shimin Yu、Lili Zhao、Shaomeng Wang、Hong-Min Liu、Zhenhe Suo、Wen Zhao

  DOI：10.1021/acs.jmedchem.9b00003

  日期：2019.6.13

  in cullin neddylation 1 (DCN1), as a co-E3 ligase, interacts with UBE2M to enhance the activation of CRLs, and this interaction is emerging as a therapeutic target for human diseases. Here, we present a series of pyrimidin-based small molecular inhibitors targeting DCN1-UBE2M interaction. After finding a novel inhibitor DC-1 with IC50 = 1.2 μM, we performed a series of chemical optimizations, which finally

  Cullin-RING E3 连接酶 (CRL) 的 Neddylation 调节大约 20% 的细胞蛋白的稳态。cullin neddylation 1 (DCN1) 缺陷作为一种 co-E3 连接酶，与 UBE2M 相互作用以增强 CRL 的激活，这种相互作用正在成为人类疾病的治疗靶点。在这里，我们提出了一系列针对 DCN1-UBE2M 相互作用的基于嘧啶的小分子抑制剂。在找到 IC50 = 1.2 μM 的新型抑制剂 DC-1 后，我们进行了一系列化学优化，最终发现了一种含有 5-氰基-6-苯基嘧啶基抑制剂 DC-2 (IC50 = 15) 的强效噻唑纳米）。接下来，使用蛋白质和细胞热位移分析、免疫共沉淀、分子对接和位点特异性突变实验，我们进一步证明 DC-2 在分子和细胞水平上特异性抑制 UBE2M 和 DCN1 的相互作用，导致 cullin3 的 neddylation 减少和其底物
• Design, Synthesis and In Vitro Evaluation of 4-Oxo-6-Substituted Phenyl- 2-Thioxo1,2,3,4-Tetrahydropyrimidine-5-Carbonitrile Derivatives as HIV Integrase Strand Transfer Inhibitors
  作者：Pankaj Wadhwa、Priti Jain、Hemant R. Jadhav

  DOI：10.2174/1570180817999201022193325

  日期：2021.4

  Aim: To design, synthesis and in vitro evaluation of 4-oxo-6-substituted phenyl-2- thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives as HIV integrase strand transfer inhibitors. Background: Human immunodeficiency virus-1 (HIV-1), a member of retroviridae family, is the primary causative agent of acquired immunodeficiency syndrome (AIDS). Three enzymes viz: integrase (IN), reverse transcriptase

  目的：设计，合成和体外评估4-羟基-取代的苯基-2-硫代1,2,3,4-四氢嘧啶-5-甲腈衍生物作为HIV整合酶链转移抑制剂。 背景：人类免疫缺陷病毒1（HIV-1）是逆转录病毒科的成员，是获得性免疫缺陷综合症（AIDS）的主要病原体。三种酶：整合酶（IN），逆转录酶（RT）和蛋白酶在其复制周期中起重要作用。HIV-1整合酶负责催化两个独立的反应，即3'-加工（3'-P）和链转移（ST），将病毒DNA掺入人染色体DNA中，这被认为是“不可逆转的点”在HIV感染中。
• Design, synthesis, molecular modelling, and biological evaluation of novel substituted pyrimidine derivatives as potential anticancer agents for hepatocellular carcinoma
  作者：Naglaa Mohamed Ahmed、Mahmoud Youns、Moustafa Khames Soltan、Ahmed Mohammed Said

  DOI：10.1080/14756366.2019.1612889

  日期：2019.1.1

  Abstract New anticancer agents are highly needed to overcome cancer cell resistance. A novel series of pyrimidine pyrazoline-anthracene derivatives (PPADs) (4a-t) were designed and synthesised. The anti-liver cancer activity of all compounds was screened in vitro against two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh-7) as well as normal fibroblast cells by resazurin assay. The designed

  抽象的 迫切需要新的抗癌药来克服癌细胞的耐药性。设计并合成了一系列新的嘧啶吡唑啉-蒽衍生物（PPADs）（4a-t）。通过刃天青测定，体外针对两种肝细胞癌（HCC）细胞系（HepG2和Huh-7）以及正常成纤维细胞筛选了所有化合物的抗肝癌活性。设计的化合物4a-t对这两种细胞系表现出广谱抗癌活性，与正常细胞相比，它们的活性在癌症上更为突出。化合物4e对HepG2和Huh-7细胞系显示出高效力（（ IC 50分别相当于阿霉素（DOX）活性的5.34和6.13μg/ mL）。已经研究了结构活性关系（SAR），化合物4e，4i，4m和4q是最有前途的抗癌药物。这些化合物通过在所有测试浓度下均显着激活caspase 3/7来诱导HepG2和Huh-7细胞凋亡。总之，4e可能是一种有效的抗癌药。
• 2-Thiopyrimidinones as therapeutic agents
  申请人：Sikorski A. James

  公开号：US20060100226A1

  公开（公告）日：2006-05-11

  The present invention provides compounds of Formulas I-VII, or pharmaceutically acceptable derivatives thereof, wherein the compounds are as defined in the specification. These compounds are inhibitors of protein kinases, particularly inhibitors of MEKK protein kinases. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders, such as inflammatory disorders.

  本发明提供了I-VII式化合物或其药学上可接受的衍生物，其中所述化合物如规范中所定义。这些化合物是蛋白激酶的抑制剂，特别是MEKK蛋白激酶的抑制剂。本发明还提供了包含本发明化合物的药学上可接受的组合物以及利用这些化合物和组合物治疗各种蛋白激酶介导的疾病的方法，例如炎症性疾病。
• Metal-organic framework (ZIF-8) for Knoevenagel condensation and multi-components Biginelli Reaction
  作者：Mostafa Sayed、Ahmed Soliman、Hani Nasser Abdelhamid

  DOI：10.1016/j.jssc.2023.124534

  日期：2024.4

  numerous advantages in the realm of organic synthesis, particularly in the construction of physiologically active organic blocks. This study utilized zeolitic imidazolate framework-8 (ZIF-8) as a heterogeneous catalyst in the Knoevenagel condensation and Biginelli reaction. ZIF-8 was synthesized under varying conditions, both in the presence and absence of guest molecules such as benzoic acid, terephthalic

  金属有机框架（MOF）是一种多相催化剂，在有机合成领域，特别是在构建生理活性有机嵌段方面具有众多优势。本研究利用咪唑骨架沸石 8 (ZIF-8) 作为 Knoevenagel 缩合和 Biginelli 反应中的多相催化剂。ZIF-8 是在不同条件下合成的，包括存在和不存在客体分子（例如苯甲酸、对苯二甲酸和碳酸盐）。研究了通过使用不同的醛与丙二腈或氰基乙酸乙酯组合来合成各种α,β-不饱和腈或酯。研究了 ZIF-8 对反应产率的影响，并评估了广泛的底物范围。此外，ZIF-8在Biginelli反应中的应用在多种二氢嘧啶酮/硫酮的合成中表现出显着的催化功效。ZIF-8 材料的产率高于 99%。在五个周期内检查了催化剂的可回收性，结果表明催化剂的反应活性没有显着下降。