Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives Journal Articles uri icon

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abstract

  • Substitution at the 7-position of the chromen-4-one pharmacophore of 8-(dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one NU7441, a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, with allyl, n-propyl or methyl enabled the resolution by chiral HPLC of atropisomers. 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.

authors

  • Clapham, Kate M
  • Rennison, Tommy
  • Jones, Gavin
  • Craven, Faye
  • Bardos, Julia
  • Golding, Brian
  • Griffin, Roger J
  • Haggerty, Karen
  • Hardcastle, Ian R
  • Thommes, Pia
  • Ting, Attilla
  • Cano, Céline

publication date

  • 2012