2-Morpholin-4-yl-8-thiophen-3-ylchromen-4-one | 503468-85-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-Morpholin-4-yl-8-thiophen-3-ylchromen-4-one
• CAS: 503468-85-7
• 化学式: C₁₇H₁₅NO₃S
• 分子量: 313.377
• InChiKey: MHMBRJOWOVNUNC-UHFFFAOYSA-N

物化性质

• 沸点：
  471.9±45.0 °C(Predicted)
• 密度：
  1.350±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  67
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-乙酰基吗啉 在 四(三苯基膦)钯 、 三氟甲磺酸酐 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 2-Morpholin-4-yl-8-thiophen-3-ylchromen-4-one
  参考文献：
  名称：

  Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries

  摘要：

  A solution-phase multiple-parallel synthesis approach was employed for the preparation of 6-, 7- and 8-aryl-substituted chromenone libraries. which were screened as inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). These studies resulted in the identification of 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) as a highly potent and selective DNA-PK inhibitor (IC50 = 14nM), exhibiting ATP-competitive inhibition kinetics. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.09.060

文献信息

• Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries
  作者：Justin J.J. Leahy、Bernard T. Golding、Roger J. Griffin、Ian R. Hardcastle、Caroline Richardson、Laurent Rigoreau、Graeme C.M. Smith

  DOI：10.1016/j.bmcl.2004.09.060

  日期：2004.12

  A solution-phase multiple-parallel synthesis approach was employed for the preparation of 6-, 7- and 8-aryl-substituted chromenone libraries. which were screened as inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). These studies resulted in the identification of 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) as a highly potent and selective DNA-PK inhibitor (IC50 = 14nM), exhibiting ATP-competitive inhibition kinetics. (C) 2004 Elsevier Ltd. All rights reserved.
• Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach
  作者：Ian R. Hardcastle、Xiaoling Cockcroft、Nicola J. Curtin、Marine Desage El-Murr、Justin J. J. Leahy、Martin Stockley、Bernard T. Golding、Laurent Rigoreau、Caroline Richardson、Graeme C. M. Smith、Roger J. Griffin

  DOI：10.1021/jm050444b

  日期：2005.12.1

  Structure-activity relationships for inhibition of DNA-dependent protein kinase (DNA-PK) have been defined for substituted chromen-4-ones. For the 2-amino-substituted benzo[h]chromen-4-ones, a morpholine substituent at this position was essential for activity. Small libraries of 6- and 7-alkoxy-substituted chromen-4-ones showed that a number of 7-alkoxysubstituted chromenones displayed improved activity. Focused libraries incorporating 6-, 7-, and 8-aryl and heteroaryl substituents were prepared. In these cases, 6- and 7-substitution was disfavored, whereas 8-substitution was largely tolerated. Surprisingly, two compounds, 2-N-morpholino-8-dibenzofuranyl-chromen-4-one (NU7427, 3238}) and the 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one (NU7441, 3226}) were excellent inhibitors (IC50 vs DNAPK = 40 and 13 nM, respectively). The ring-saturated analogue 2-N-morpholino-8-(6',7',8',9'-tetrahydrodibenzothiophene)chromen-4-one, 36, retained potent activity (IC50 vs DNA-PK = 23 nM). The dibenzothiophene 3238} sensitized HeLa cells to ionizing radiation in vitro, with dose modification factors of 2.5 at 10% survival being observed at 0.5 mu M. The cytotoxicity of the topoisomerase II inhibitor etoposide was also potentiated.