3-(4-methyl-1,3-thiazol-2-yl)-7-hydroxycoumarin | 313375-56-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-(4-methyl-1,3-thiazol-2-yl)-7-hydroxycoumarin
• 英文别名: 7-Hydroxy-3-(4-methyl-thiazol-2-yl)-chromen-2-one；7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)chromen-2-one
• CAS: 313375-56-3
• 化学式: C₁₃H₉NO₃S
• 分子量: 259.285
• InChiKey: KPQSZJRCWYCLHO-UHFFFAOYSA-N

物化性质

• 熔点：
  295-296 °C(Solv: N,N-dimethylformamide (68-12-2))
• 沸点：
  523.7±60.0 °C(Predicted)
• 密度：
  1.467±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  87.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(4-methyl-1,3-thiazol-2-yl)-7-hydroxycoumarin 在 15-冠醚-5 、 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 12.0h， 生成 3-(4-methylthiazolyl-2)-7-(2-acetamido-2-deoxy-β-D-glucopyranosyloxy)coumarin
  参考文献：
  名称：

  摘要：

  beta-0-Glycosides of N-acetylglucosamine with substituted 7-hydroxychromones and 7-hydroxycoumarins as the aglycones are synthesized The phenyl hydroxyls are O-glycosylated in a solid-liquid system with crown-ether catalysts. The structures of the chromone and coumarin N-acetylglucosaminides and their per-0-acetates are proved by PMR spectroscopy.

  DOI：

  10.1023/a:1019635914082
• 作为产物：
  描述：

  (4-甲基-1,3-噻唑-2-基)乙腈 在 哌啶 、 硫酸 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 3-(4-methyl-1,3-thiazol-2-yl)-7-hydroxycoumarin
  参考文献：
  名称：

  多官能吡唑。3. 3-（3-芳基-4-甲酰基-1-吡唑基）丙酸及其酰胺的合成

  摘要：

  DOI：

  10.1007/s10593-005-0004-z

文献信息

• Aminomethylation of cytisine by 3-hetaryl-7-hydroxycoumarins
  作者：M. S. Frasinyuk、A. V. Turov、V. I. Vinogradova、V. P. Khilya

  DOI：10.1007/s10600-007-0073-6

  日期：2007.3

  8-Aminomethyl derivatives of 7-hydroxycoumarins were prepared by reaction of methylene-bis-cytisine and substituted 7-hydroxycoumarins.

  通过亚甲基双氧野靛碱与取代的7-羟基香豆素的反应，制备了8-氨基甲基衍生物的7-羟基香豆素。
• A TPD-MS study of the interaction of coumarins and their heterocyclic derivatives with a surface of fumed silica and nanosized oxides CeO2/SiO2, TiO2/SiO2, Al2O3/SiO2
  作者：Kostiantyn Kulyk、Valentyna Ishchenko、Borys Palyanytsya、Volodymyr Khylya、Mykola Borysenko、Tetiana Kulyk

  DOI：10.1002/jms.1765

  日期：——

  The interactions between coumarins and the surface of fumed SiO2, CeO2/SiO2, TiO2/SiO2 and Al2O3/SiO2 were assessed by means of temperature-programed desorption mass spectrometry. The different stages of the thermolysis of coumarin were identified and an analysis of the underlying reactions was performed. The kinetic parameters of the involved reactions were thus obtained. The decomposition of thiazolyl-substituted coumarins was found to proceed through a ‘thiazole–thiazine’ ring expansion in the adsorbed state. A linear correlation between the sigma constants (Σσ) of the coumarin substituents and the activation energy of CO2 formation was obtained. Copyright © 2010 John Wiley & Sons, Ltd.

  利用程序升温脱附质谱技术，评估了香豆素与气相二氧化硅、氧化铈/二氧化硅、二氧化钛/二氧化硅以及氧化铝/二氧化硅表面的相互作用。鉴别出香豆素热解的不同阶段，并进行了基础反应的分析。从而获得了相关反应的动力学参数。发现噻唑取代的香豆素在吸附状态下通过“噻唑-噻嗪”环扩展进行分解。获得了香豆素取代基的sigma常数（Σσ）与CO2形成活化能之间的线性关系。版权所有 © 2010 John Wiley & Sons, Ltd.
• Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents
  作者：Mykhaylo Frasinyuk、Dimple Chhabria、Victor Kartsev、Haritha Dilip、Samvel N. Sirakanyan、Sivapriya Kirubakaran、Anthi Petrou、Athina Geronikaki、Domenico Spinelli

  DOI：10.3390/molecules27144637

  日期：——

  Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.

  尽管进行了广泛的研究并存在许多不同的抗癌剂，但癌症治疗仍然是一个严重和具有挑战性的问题。因此，开发具有更好治疗效果和更少副作用的新型抗癌药物以对抗这种持久的疾病仍然是必要的。在本研究中，我们报道了一系列新型苯并噻唑和色酮衍生物，这些衍生物被合成并评估其作为DDR途径的主调节因子ATR激酶抑制剂的抗癌活性。使用MTT测定法在HCT116和HeLa细胞系中对25种化合物的细胞存活率进行了测试，这涉及到将化合物在最终浓度为10µM的条件下孵育72小时。发现孵育化合物2c、7h和7l的细胞的存活率≤50％，因此这些化合物被用于剂量反应研究。在测试的化合物中，其中三种（2c、7h和7l）显示出更高的效力，其中化合物7l在两种细胞系中都表现出最佳的IC50值。发现化合物2c和7l对HCT116和HeLa两种细胞系同样具有细胞毒性，而化合物7h对HeLa细胞系的细胞毒性更好。对于这三种化合物，进行了免疫印迹分析，以分析在HeLa和HCT116细胞中Chk1在Ser 317处的磷酸化抑制。发现化合物7h在3.995µM的浓度下可抑制HeLa细胞中的pChk1在Ser 317处的磷酸化。在用各种浓度的3种化合物（2、5和10µM）处理HeLa细胞时，进一步分析了Chk1和pChk1的表达，其中化合物7h在2和5µM的浓度下表现出Chk1的抑制作用，而化合物7l在5µM的浓度下观察到pChk1的表达。为了支持这些结果，通过分子对接研究了化合物与ATR激酶结构域的结合相互作用，发现化合物2c、7h和7l的结合相互作用类似于已知的mTOR/ATR抑制剂Torin2。对这组分子的进一步研究正在进行，以了解它们对ATR途径的特异性。
• Chemistry of 3-hetarylcoumarins. 2*. 3-(2-thiazolyl)coumarins
  作者：O. V. Khilya、O. V. Shablykina、M. S. Frasinyuk、A V. Turov、V. V. Ishchenko、V. P. Khilya

  DOI：10.1007/s10593-005-0004-z

  日期：2004.11
• ——
  作者：A. E. Zemlyakov、V. O. Kur'yanov、T. A. Chupakhina、V. Ya. Chirva、V. V. Ishchenko、M. M. Garazd、V. P. Khilya

  DOI：10.1023/a:1019635914082

  日期：——

  beta-0-Glycosides of N-acetylglucosamine with substituted 7-hydroxychromones and 7-hydroxycoumarins as the aglycones are synthesized The phenyl hydroxyls are O-glycosylated in a solid-liquid system with crown-ether catalysts. The structures of the chromone and coumarin N-acetylglucosaminides and their per-0-acetates are proved by PMR spectroscopy.