4‐chloro‐2‐(methylthio)‐6‐(thien‐2‐yl)‐pyrimidine‐5‐carbonitrile | 439808-45-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4‐chloro‐2‐(methylthio)‐6‐(thien‐2‐yl)‐pyrimidine‐5‐carbonitrile
• 英文别名: 4-chloro-2-methylsulfanyl-6-(2-thienyl) pyrimidne-5-carbonitirle；4-Chloro-2-methylsulfanyl-6-thiophen-2-ylpyrimidine-5-carbonitrile
• CAS: 439808-45-4
• 化学式: C₁₀H₆ClN₃S₂
• 分子量: 267.763
• InChiKey: QFDZILYOGDUWJG-UHFFFAOYSA-N

物化性质

• 沸点：
  472.5±45.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  103
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4‐chloro‐2‐(methylthio)‐6‐(thien‐2‐yl)‐pyrimidine‐5‐carbonitrile 在 一水合肼 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 生成 2,6-dihydrazino-4-(2-thienyl)pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Ahmed, Gamal A.; Abd El-Salam, Nasser M., Bollettino Chimico Farmaceutico, 2003, vol. 142, # 3, p. 115 - 118

  摘要：

  DOI：
• 作为产物：
  描述：

  2-疏基-6-氧代-4-(2-噻吩)-1,6-二氢嘧啶-5-甲腈 在 potassium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 4‐chloro‐2‐(methylthio)‐6‐(thien‐2‐yl)‐pyrimidine‐5‐carbonitrile
  参考文献：
  名称：

  Chloropyrimidines as a new class of antimicrobial agents

  摘要：

  In the course of our investigations of pyrimidines as antimycotic agents, we have identified a sub-class, with significant in vitro activity against mycobacteria. The salient feature of these pyrimidine derivatives (3a-o and 7a,b) is their appended aryl, heteroaryl and alkylthio substituent at position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of Mycobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 mug/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 mug/ mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 mug/mL. All the synthesized compounds were also evaluated for their antimycotic activity against five pathogenic fungi but only some of them 3j-n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00374-1

文献信息

• Synthesis and in vitro investigation of novel cytotoxic pyrimidine and pyrazolopyrimidne derivatives showing apoptotic effect
  作者：Fatma A. Ragab、Yassin M. Nissan、Emad M. Seif、Ahmed Maher、Reem K. Arafa

  DOI：10.1016/j.bioorg.2020.103621

  日期：2020.3

  A series of novel derivatives of hydrazinylpyrimidines, pyrazolylpyrimidines and 3-amino[3,4-d]pyrazolopyrimidines have been synthesized and tested for their in vitro cytotoxic activity against 60 tumor cell lines by NCI. The in vitro cytotoxic IC50 values for the most active compounds were determined against the colon-KM12 cell line (5d, 7c and 7d), breast-MCF-7 (6a) and melanoma-MDA-MB-435 (6h) using

  已经合成了一系列新颖的肼基嘧啶，吡唑基嘧啶和3-氨基[3,4-d]吡唑并嘧啶衍生物，并通过NCI测试了它们对60种肿瘤细胞系的体外细胞毒性活性。确定了活性最高的化合物在体外对结肠KM12细胞系（5d，7c和7d），乳腺癌MCF-7（6a）和黑素瘤-MDA-MB-435（6h）的体外细胞毒性IC50值。氟尿嘧啶（5-FU）作为阳性对照。发现衍生物5d和7c是对KM12细胞系最有效的衍生物（分别为IC50 = 1.73和1.21 µM），与5-FU（IC50 = 12.26）相比，具有较高的选择性指数（SI）（分别为18.82和35.49）。 µM，SI = 1.93）。进一步研究化合物5d和7c在KM12细胞系中的凋亡行为。研究表明，caspase 3/9和促凋亡因子Bax上调。另一方面，抗凋亡因子Bcl-2的表达及其在纳摩尔浓度下的抑制被下调。此外，使用膜联蛋白V-FITC染色法检测了KM12细胞中衍生物5d和7c的凋亡作用。
• New functionalized 6‐thienylpyrimidine‐5‐carbonitriles as antiproliferative agents against human breast cancer cells
  作者：Omaima M. AboulWafa、Hoda M. G. Daabees、Ali Hammad、Waleed A. Badawi

  DOI：10.1002/ardp.202100177

  日期：2021.11

  the tested compounds did not show significant inhibition, and it can be assumed that they exert their antiproliferative activity through different target mechanisms. In addition, caspase-9 protein activation assays, cell cycle analysis using flow cytometry, and annexin V-fluorescein isothiocyanate–propidium iodide (FITC/PI) dual staining assays were performed for the most active compounds. All the tested

  合成了 6-噻吩基嘧啶-5-腈衍生物，并筛选了它们对两种人乳腺癌细胞系的体外抗增殖活性，并与 5-氟尿嘧啶作为参考进行了比较。化合物2、3a - c和6b演变为对两种细胞系最活跃的同系物，而其他化合物仅对一种细胞系显示出选择性。化合物2通过抑制表皮生长因子受体 (EGFR) 发挥作用，而6b显示出比来曲唑更低的芳香酶抑制活性。其余的测试化合物没有显示出显着的抑制作用，可以假设它们通过不同的靶点机制发挥其抗增殖活性。此外，对最具活性的化合物进行了 caspase-9 蛋白活化测定、使用流式细胞术的细胞周期分析和膜联蛋白 V-异硫氰酸荧光素-碘化丙啶 (FITC/PI) 双染色测定。发现所有测试的化合物都是有效的嘧啶衍生物，能够在 MCF-7 和 MDA-MB-231 细胞中启动细胞凋亡。