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

@article{Hardcastle2005DiscoveryOP,
  title={Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach.},
  author={Ian R Hardcastle and Xiao-ling Cockcroft and Nicola J. Curtin and Marine Desage El-Murr and Justin J. J. Leahy and Martin Stockley and Bernard T Golding and Laurent Jean Martin Rigoreau and Caroline J. Richardson and Graeme C M Smith and Roger John Griffin},
  journal={Journal of medicinal chemistry},
  year={2005},
  volume={48 24},
  pages={
          7829-46
        }
}
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… Expand
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TLDR
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TLDR
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TLDR
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Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives.
TLDR
Biological evaluation against DNA-PK of each pair of atropisomers showed a marked difference in potency, with biological activity residing exclusively in the laevorotatory enantiomer. Expand
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