Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 14, Issue 24, Pages 6083-6087Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2004.09.060
Keywords
chromenones; DNA repair; DNA-PK; inhibitors
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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.
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