DNA-PK inhibitors

Details DNA-PK inhibitors DNA-PK inhibitors

2008-07-22

2008-07-22

Saeed, Kamal A. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C549S043000

Reexamination Certificate

active

07402607

ABSTRACT:
A compound of formula I:and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein:R1and R2are independently selected from hydrogen, an optionally substituted C1-7alkyl group, C3-20heterocyclyl group, or C5-20aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; Q is —NH—C(═O)— or —O—; Y is an optionally substituted C1-5alkylene group; X is selected from SR3or NR4R5, wherein, R3, or R4and R5are independently selected from hydrogen, optionally substituted C1-7alkyl, C5-20aryl, or C3-20heterocyclyl groups, or R4and R5may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms;if Q is —O—, X is additionally selected from —C(═O)—NR6R7, wherein R6and R7are independently selected from hydrogen, optionally substituted C1-7alkyl, C5-20aryl, or C3-20heterocyclyl groups, or R6and R7may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms;and if Q is —NH—C(═O)—, —Y—X may additionally be selected from C1-7alkyl.

REFERENCES:
patent: 4954518 (1990-09-01), Takano et al.
patent: 5252735 (1993-10-01), Morris
patent: 5284856 (1994-02-01), Naik et al.
patent: 5302613 (1994-04-01), Morris
patent: 5703075 (1997-12-01), Gammill et al.
patent: 5733920 (1998-03-01), Mansuri et al.
patent: 5922755 (1999-07-01), Tanaka et al.
patent: 6348311 (2002-02-01), Kastan et al.
patent: 6387640 (2002-05-01), Kastan et al.
patent: 2004/0002492 (2004-01-01), Smith et al.
patent: 2004/0023968 (2004-02-01), Martin et al.
patent: 2004/0192687 (2004-09-01), Martin et al.
patent: 2005/0054657 (2005-03-01), Smith et al.
patent: 2005/0107367 (2005-05-01), Martin et al.
patent: 2006/0178361 (2006-08-01), Hummersone et al.
patent: 0 610 519 (1994-08-01), None
patent: 0 635 268 (1995-01-01), None
patent: 0 640 339 (1995-03-01), None
patent: 0 641 566 (1995-03-01), None
patent: 0 648 492 (1995-04-01), None
patent: 0 658 343 (1995-06-01), None
patent: 1303724 (1973-01-01), None
patent: 2 302 021 (1997-01-01), None
patent: 03215-423 (1990-01-01), None
patent: WO 90/06921 (1990-06-01), None
patent: WO 91/19707 (1991-12-01), None
patent: WO 92/00290 (1992-01-01), None
patent: WO 95/29673 (1995-11-01), None
patent: WO 96/01108 (1996-01-01), None
patent: WO 97/15658 (1997-05-01), None
patent: WO 97/18323 (1997-05-01), None
patent: WO 98/55602 (1998-12-01), None
patent: WO 98/56391 (1998-12-01), None
patent: WO 99/47494 (1999-09-01), None
patent: WO 01/53266 (2001-07-01), None
patent: WO 02/20500 (2002-03-01), None
patent: WO 02/056912 (2002-07-01), None
patent: WO 03/024949 (2003-03-01), None
patent: WO 03/093261 (2003-04-01), None
patent: WO 03/034997 (2003-05-01), None
patent: WO 03/035618 (2003-05-01), None
patent: WO 03/070726 (2003-08-01), None
patent: 2006032869 (2006-03-01), None
Abraham, Robert T., “Cell cycle checkpoint signaling through the ATM and ATR kinases,”Genes&Dev., 15: 2177-2196 (2001).
Archer, S. et al., “Ring-Hydroxylated Analogues of Lucanthone as Antitumore Agents,”J. Med Chem., 25, 220-227 (1982).
Banin, S., et al., “Enhanced phosphorylation of p53 by ATM in response to DNA damage,”Science, 281:1674-1677 (1998).
Bantick, J.R., et al., “Synthesis of 2-aminochromones,”J. Heterocyclic Chem., 1981, vol. 18, pp. 679-684.
Berge, Stephen M., et al., “Review article,”J. Pharm. Sci., 66:1, pp. 1-19 (1977).
Bettoni, et al., “Synthesis and absolute configuration of substituted morpholines,”Tetrahedron, 1980, vol. 36, pp. 409-415.
Boyd, J., et al., “The chemistry of the ‘insoluble red’ woods,”J. Chem. Soc., 1948, pp. 174-176.
Brown, P.O., “Integration of retroviral DNA,”Curr Top Microbiol Immunol., 157:19-48 (1990).
Buon, C., et al., “Synthesis of 3-substituted and 2,3-disubstituted-4H-1,4-Benzoxazines,”Tetrahedron, 2000, vol. 56, pp. 605-614.
Chiosis, G, et al. “LY294002-geldanamycin heterodiamers as selective inhibitors of the PI3K and PI3k-related family”,Bioorganic&Medicinal Chemistry Letters, vol. 11, No. 7, Apr. 9, 2001 pp. 909-913, XP004232522.
Daniel, R., et al., “A role for DNA-PK in retroviral DNA integration,”Science, 1999, vol. 284, pp. 644-647.
Daniel, Rene, et al., “Wortmannin potentiates integrase-mediated killing of lymphocytes and reduces the efficiency of stable transduction by retroviruses,”Mol. Cell Biol, 21:4, 1164-1172 (2001).
Datta, A., et al., “Reformatsky reaction on aroylketene S, N-acetals: a facile route to 4-amino-6-aryl-2H-pyran-2-ones,”Synthesis, 1988, vol. 3, pp. 248-250.
Di Braccio, M., et al., “1,2-fused pyrimidines VII,”Eur. J. Med., Chem., 1995, vol. 30, No. 1, pp. 27-38.
Di Braccio, M., et al., “Pyran derivatives XIX. (Dialkylamino) substituted 1-benzopyranones and naphthopyranoes with platelet antiaggregating activity,”Farmaco, 1995, vol. 50, No. 10, pp. 703-711.
Durocher, Daniel, and Jackson, Stephen P., “DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?,”Curr Opin Cell Biol., 13:225-231 (2001).
Ermili, A., et al., “Chemical and pharmacological research on pyran derivatives,” Enclosed:Chemical Abstracts, 1977, vol. 87, No. 15, p. 588 (XP-002218602), 117750g.
Gell, D., et al., “Mapping of protein-protein interactions within the DNA-dependent protein kinase complex,”Nucleic Acid Res., 1999, vol. 27, No. 17, pp. 3494-3502.
Giroux, A., et al, “One pot biaryl synthesis via in situ boronate formation,”Tet. Lett., 38:22, 3841-3844 (1997).
Goytisolo, et al., “The absence of DNA-dependent protein kinase catalytic subunit in mice results in anaphase bridges and in increased telomeric fusions with normal telomere length and G-strand overhang,”Mol. Cell. Biol., 2001, vol. 21, No. 11, pp. 3642-3651.
Green, T. and Wuts, P., ed.,Protective Groups in Organic Synthesis, Wiley (1999).
Griffin, et al., “Selective Benzopyranone and Pyrimido [2,1-a]isoquinolin-4-one Inhibitors of DNA-Dependent Protein Kinase: Synthesis, Structure—Activity Studies, and Radiosensitization of a Humn Tumor Cell Line in Vitro”,J. Med. Chem., 2005, 48, 569-585.
Hartley, K. O., et al., “DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telengiectasia gene product,”Cell, 1995, vol. 82, pp. 849-856.
Haselhorst, Dorte, et al., “Development of cell lines stably expressing human immunodeficiency virus type 1 proteins for studies in encapsidation and gene transfer,”J Gen Virol, 79: 231-237 (1998).
Herzog, Karl-Heinz et al., “Requirement for ATM in ionizing radiation-induced cell death in the developing central nervous system,”Science, 280: 1089-1091 (1998).
Hickson, Ian, et al, “Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM,”Cancer Research 64, Dec. 15, 2004, 9152-9159.
Hollick, J J, et al., “2,6-Disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-dependent protein kinase”Bioorganic and Medicinal Chemistry Letters, vol. 13, No. 18, Sep. 15, 2003 pp. 3083-3086, XP002303369.
Ishiyama, T. et al., “Synthesis of arylboronates via the palladium(0)-catalyzed cross-coupling reaction of tetra(alkoxo)diborons with aryl triflates,”Tett. Lett., 38:19, 3447-3450 (1997).
Ismail, I.H. et al., Oncogene (2004) 23:873-883.
Izzard, R.A., et al., “Competitive & noncompetitive inhibition of the DNA-dependent protein kinase,”Cancer Research, 1999, vol. 59, No. 11, pp. 2581-2586.
Jackson, S. P., “DNA damage detection by DNA dependent p

Affiliated with

Also associated with

Rating

DNA-PK inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with DNA-PK inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and DNA-PK inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2790328