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

KM Clapham, T Rennison, G Jones, F Craven…

Index: Clapham, Kate M.; Rennison, Tommy; Jones, Gavin; Craven, Faye; Bardos, Julia; Golding, Bernard T.; Griffin, Roger J.; Haggerty, Karen; Hardcastle, Ian R.; Thommes, Pia; Ting, Attilla; Cano, Celine Organic and Biomolecular Chemistry, 2012 , vol. 10, # 33 p. 6747 - 6757

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Citation Number: 9

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 ...