2,6-disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-Dependent protein kinase (DNA-PK).

@article{Hollick200326disubstitutedPA,
  title={2,6-disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-Dependent protein kinase (DNA-PK).},
  author={Jonathan James Hollick and Bernard T Golding and Ian R Hardcastle and Niall M. B. Martin and Caroline J. Richardson and Laurent Jean Martin Rigoreau and Graeme C M Smith and Roger John Griffin},
  journal={Bioorganic \& medicinal chemistry letters},
  year={2003},
  volume={13 18},
  pages={
          3083-6
        }
}
6-aryl-2-morpholin-4-yl-4H-pyran-4-ones and 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones were synthesised and evaluated as potential inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Several compounds in each series exhibited superior activity to the chromenone LY294002, and were of comparable potency to the benzochromenone NU7026 (IC(50)=0.23 microM). Importantly, members of both structural classes were found to be selective inhibitors of DNA-PK over related… Expand
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One such compound, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, LY294002, completely and specifically abolished PtdIns 3-kinase activity, which may be beneficial in the treatment of proliferative diseases as well as in elucidating the biological role of the kinase in cellular proliferation and growth factor response. Expand
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