Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives.

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.

DOI: 10.1039/c2ob26035b

Cite this paper

@article{Clapham2012PotentEI, title={Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives.}, author={Kate M Clapham and Tommy Rennison and Gavin C. Jones and Faye L Craven and Julia Bardos and Bernard T. Golding and Roger J. Griffin and Karen Haggerty and Ian R. Hardcastle and Pia A Thommes and Attilla Ting and C{\'e}line Cano}, journal={Organic & biomolecular chemistry}, year={2012}, volume={10 33}, pages={6747-57} }