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

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

Newcastle Cancer Centre, Northern Institute for Cancer Research, School of Chemistry, Newcastle University, Newcastle upon Tyne, UK.

Organic & biomolecular chemistry 2012 Sep 7

filter terms:

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.

Citation

Kate M Clapham, Tommy Rennison, Gavin Jones, Faye Craven, Julia Bardos, Bernard T Golding, Roger J Griffin, Karen Haggerty, Ian R Hardcastle, Pia Thommes, Attilla Ting, Céline Cano. Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives. Organic & biomolecular chemistry. 2012 Sep 7;10(33):6747-57