4,4,5,5-tetramethyl-2-(6,7,8,9-tetrahydrodibenzothiophen-4-yl)-[1,2,3]dioxaborolane | 870297-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 4,4,5,5-tetramethyl-2-(6,7,8,9-tetrahydrodibenzothiophen-4-yl)-[1,2,3]dioxaborolane
• 英文别名: 4,4,5,5-Tetramethyl-2-(6,7,8,9-tetrahydrodibenzothiophen-4-yl)-1,3,2-dioxaborolane
• CAS: 870297-92-0
• 化学式: C₁₈H₂₃BO₂S
• 分子量: 314.256
• InChiKey: NACUJBOUFLGYAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  46.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,4,5,5-tetramethyl-2-(6,7,8,9-tetrahydrodibenzothiophen-4-yl)-[1,2,3]dioxaborolane 、 2-morpholin-4-yl-4-oxo-4H-chromen-8-yl trifluoromethanesulfonate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以25%的产率得到2-morpholin-4-yl-8-(6',7',8',9'-tetrahydrodibenzothiophen-4'-yl)chromen-4-one
  参考文献：
  名称：

  Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach

  摘要：

  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, 32{38}) and the 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one (NU7441, 32{26}) 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 32{38} 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.

  DOI：

  10.1021/jm050444b
• 作为产物：
  描述：

  2-氯环己酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium hydroxide 、 PPA 、 potassium acetate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 32.5h， 生成 4,4,5,5-tetramethyl-2-(6,7,8,9-tetrahydrodibenzothiophen-4-yl)-[1,2,3]dioxaborolane
  参考文献：
  名称：

  Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach

  摘要：

  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, 32{38}) and the 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one (NU7441, 32{26}) 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 32{38} 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.

  DOI：

  10.1021/jm050444b