PI-3 kinase inhibitor prodrugs

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C514S232500, C514S320000, C514S392000, C514S429000, C514S453000, C514S459000, C540S450000, C540S467000, C544S150000, C544S151000, C546S196000, C548S229000, C548S528000, C549S315000, C549S347000, C549S383000, C549S401000, C549S403000, C558S013000, C424S001210, C424S450000

Reexamination Certificate

active

06949537

ABSTRACT:
The invention provides novel prodrugs of inhibitors of PI-3 kinase. The novel compounds are LY294002 and analogs thereof comprising a reversibly quaternized amine.

REFERENCES:
patent: 3937719 (1976-02-01), Sellstedt et al.
patent: 5116954 (1992-05-01), Briet et al.
patent: WO 91/19707 (1991-12-01), None
patent: WO 01/53266 (2001-07-01), None
patent: WO 03/024949 (2003-03-01), None
Bantick, J., et al., “Synthesis of 2-Aminochromones, Studies on the Nucleophilic Displacement of Sulphinyl and Sulphonyl Groups in the 2-Position of 5,8-Dimethoxychromone,” J. Het. Chem., vol. 18, pp. 679-684 (1981).
Chiosis, G., et al., “LY294002-Geldanamycin Heterodimers as Selective Inhibitors of the PI3K and PI3K-related Family, ” Bioorganic & Medicinal Chemistry Letters, vol. 11, pp. 909-913 (2001).
Vlahos, C., et al., “A Specific Inhibitor of Phosphatidylinositol 3-Kinase, 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)” Journal of Biological Chemistry, vol. 269, No. 7, pp. 5241-5248 (1994).
Walker, E., et al., “Structural Determinants of Phosphoinositide 3-Kinase Inhibition by Wortmannin, LY294002, Quercetin, Myricetin, and Staurosporine,” Molecular Cell, vol. 6, pp. 909-919 (2000).
Wermuth, C., et al., “Designing Prodrugs and Bioprecursors I: Carrier Prodrugs,” The Practice of Medicinal Chemistry, Academic Press Limited, pp. 671-696 (1996).
PCT International Search Report for PCT/US2004/010399 dated Aug. 12, 2004.

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