2,6-Disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-dependent protein kinase (DNA-PK)

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 18, 2003, Pages 3083-3086

  Hollick, Jonathan J ^a   Golding, Bernard T ^a   Hardcastle, Ian R ^a   Martin, Niall ^b   Richardson, Caroline ^b   Rigoreau, Laurent J M ^a,b   Smith, Graeme C M ^b   Griffin, Roger J ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b KuDOS Pharmaceuticals Limited   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 2,6 PYRAN 4 ONE INHIBITOR; BENZOCHROMENONE; CHEMICAL COMPOUND; DNA DEPENDENT PROTEIN KINASE; NU 7026; PHOSPHATIDYLINOSITOL 3 KINASE; RECEPTOR BLOCKING AGENT; THIOPYRAN 4 ONE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; COMPARATIVE STUDY; DNA LIBRARY; DNA REPAIR; DRUG POTENCY; DRUG SYNTHESIS; IC 50; METHODOLOGY; SCREENING; STRUCTURE ACTIVITY RELATION;

LATEOLABRAX JAPONICUS;

EID: 0042521121     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00652-8     Document Type: Article

References (17)

1. Doherty A.J., Jackson S.R. Curr. Biol. 11:2001;R920.
2. Smith G.C.M., Jackson S.P. Genes Dev. 13:1999;916.
3. Shiloh Y. Nat. Rev. Cancer. 3:2003;155.
4. Jackson S.P. Carcinogenesis. 23:2002;687.
5. Jackson S.P. Int. J. Biochem. Cell Biol. 29:1997;935.
6. Rosenzweig K.E., Youmell M.B., Palayoor S.T., Price B.D. Clin. Cancer Res. 3:1997;1149.
7. Boulton S., Kyle S., Durkacz B.W. Eur. J. Cancer. 36:2000;535.
8. Kim C.H., Park S.J., Lee S.H. J. Pharmacol. Exp. Ther. 303:2002;753.
9. Oliveira N.G., Castro M., Rodrigues A.S., Gil O.M., Toscano-Rico J.M., Rueff J. Teratog. Carcinog. Mutag. 22:2002;343.
10. Vlahos C.J., Matter W.F., Hui K.Y., Brown R.F. J. Biol. Chem. 269:1994;5241.
11. Ward S., Sotsios Y., Dowden J., Bruce I., Finan P. Chem. Biol. 10:2003;207. and references therein.
12. Izzard R.A., Jackson S.P., Smith G.C.M. Cancer Res. 59:1999;2581.
13. Griffin R.J., Calvert A.H., Curtin N.J., Durkacz B.W., Golding B.T., Hardcastle I.R., Leahy J.J.J., Martin N., Newell D.R., Rigoreau L., Smith G.C.M., Stockley M., Veuger S., Hickson I. Proc. Am. Assoc. Cancer Res. 43:2002;4210.
14. Morris J., Wishka D.G. Synthesis-Stuttgart. 1994;43.
15. 1H NMR, IR, UV) and analytical (elemental analysis and/or LC-MS) data fully consistent with the assigned structures.
16. 2:MeOH (3:1, 3 mL). Further purification by preparative HPLC furnished the required thiopyranones in 5-60% yield.
17. 50 values generated from these results. Full details of the assay will be published elsewhere.