503468-79-9

Upstream product

• 87199-18-6 3-hydroxyphenylboronic acid 
• 351002-11-4 trifluoromethanesulfonic acid 2-(morpholin-4-yl)-4-oxo-4H-chromen-8-yl ester 
• 1696-20-4 4-acetylmorpholine 
• 2411-83-8 methyl-2,3-dihydroxybenzoate 
• 214360-76-6 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol 
• 503469-17-8 trifluoromethanesulfonic acid 2-hydroxy-3-(3-morpholin-4-yl-3-oxopropionyl)phenyl ester 
• 351002-09-0 2-hydroxy-3-trifluoromethanesulfonyloxybenzoic acid methyl ester 

Downstream Products

• 912844-81-6 C₂₀H₁₆F₃NO₆S 

Relevant academic research and scientific papers

8-Biarylchromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK)

The synthesis and biological evaluation of libraries of 8-biarylchromen-4-ones enabled the elucidation of structure-activity relationships for inhibition of the DNA-dependent protein kinase (DNA-PK), with 8-(3-(thiophen-2-yl)phenyl)chromen-4-one and 8-(3-(thiophen-3-yl)phenyl)chromen-4-one being especially potent inhibitors.

Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach

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-alkoxy-substituted 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 DNA-PK = 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 μM. The cytotoxicity of the topoisomerase II inhibitor etoposide was also potentiated.