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

被引：13

作者：

Cano, Celine ^{[1
]}

Golding, Bernard T. ^{[1
]}

Haggerty, Karen ^{[1
]}

Hardcastle, Ian R. ^{[1
]}

Peacock, Marcus ^{[2
]}

Griffin, Roger J. ^{[1
]}

机构：

[1] Univ Newcastle, No Inst Canc Res, Sch Chem, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[2] KuDOS Pharmaceut Ltd, Cambridge CB4 0PE, England

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2010年 / 8卷 / 08期

基金：

英国工程与自然科学研究理事会;

关键词：

DIRECTED ORTHO-METALATION; HUMAN TUMOR-CELLS; STRAND BREAK; POTENT; WORTMANNIN; RADIOSENSITIZATION; IDENTIFICATION; DISCOVERY; RADIATION; LY294002;

D O I：

10.1039/b926245h

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：1922 / 1928

页数：7

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