Bioorganic & Medicinal Chemistry Letters 2004-12-20

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

Justin J J Leahy, Bernard T Golding, Roger J Griffin, Ian R Hardcastle, Caroline Richardson, Laurent Rigoreau, Graeme C M Smith

文献索引：Bioorg. Med. Chem. Lett. 14(24) , 6083-7, (2004)

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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=14 nM), exhibiting ATP-competitive inhibition kinetics.