Atropisomeric 8-arylchromen-4-ones exhibit enantioselective inhibition of the DNA-dependent protein kinase (DNA-PK)

作者：Cano Celine^*; Golding Bernard T; Haggerty Karen; Hardcastle Ian R; Peacock Marcus; Griffin Roger J

来源：Organic and Biomolecular Chemistry, 2010, 8(8): 1922-1928.

DOI：10.1039/b926245h

Substitution at the 3-position of the dibenzothiophen-4-yl ring 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 propyl, allyl or methyl enabled the separation by chiral HPLC of atropisomers. This is a consequence of restricted rotation about the dibenzothiophene-chromenone bond. Biological evaluation against DNA-PK of the pairs of atropisomers showed a marked difference in potency, with only one enantiomer being biologically active.

• 出版日期2010