4,6-disubstituted pyrimidines useful as kinase inhibitors

Details 4,6-disubstituted pyrimidines useful as kinase inhibitors 4,6-disubstituted pyrimidines useful as kinase inhibitors

2011-08-02

2011-08-02

Wilson, James O (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

C544S105000, C544S177000, C544S326000, C546S307000

Reexamination Certificate

active

07989465

ABSTRACT:
The present invention provides 4,6-disubstituted pyrimidine compounds useful as kinase inhibitors, pharmaceutically acceptable salts and compositions thereof, and methods of using the same. The present invention also provides probe compounds, such as compounds of formula V:wherein each of Ring A, Ring B, R1′, T, Rt, m, Rx, Ry, and W is described herein.

REFERENCES:
patent: 5977117 (1999-11-01), Chan et al.
patent: 5994375 (1999-11-01), Kochanny et al.
patent: 6160010 (2000-12-01), Uckun et al.
patent: 6197779 (2001-03-01), Andries et al.
patent: 6686367 (2004-02-01), Phillips
patent: 6740655 (2004-05-01), Magee et al.
patent: 7241458 (2007-07-01), Verreck et al.
patent: 7514444 (2009-04-01), Honigberg et al.
patent: 2004/0019067 (2004-01-01), Armistead et al.
patent: 2004/0023957 (2004-02-01), Wang et al.
patent: 2004/0077661 (2004-04-01), Arbiser et al.
patent: 2004/0265917 (2004-12-01), Benjamin et al.
patent: 2005/0004125 (2005-01-01), Freyne et al.
patent: 2005/0014753 (2005-01-01), Ding et al.
patent: 2006/0030018 (2006-02-01), Zuccola et al.
patent: 2006/0063789 (2006-03-01), Freyne et al.
patent: 2006/0166943 (2006-07-01), Van Roey et al.
patent: 2007/0032493 (2007-02-01), Foley et al.
patent: 2007/0043049 (2007-02-01), Bakthavatchalam et al.
patent: 2007/0099938 (2007-05-01), Ohmoto et al.
patent: 2008/0076921 (2008-03-01), Honigberg et al.
patent: 2008/0139582 (2008-06-01), Honigberg et al.
patent: 2008/0207613 (2008-08-01), Styles et al.
patent: 2008/0214501 (2008-09-01), Pan et al.
patent: 2009/0137588 (2009-05-01), Singh et al.
patent: 2009/0181987 (2009-07-01), Honigberg et al.
patent: 2010/0004270 (2010-01-01), Honigberg et al.
patent: 2010/0022561 (2010-01-01), Honigberg et al.
patent: 2010/0029610 (2010-02-01), Singh et al.
patent: 1473289 (2004-11-01), None
patent: 07041461 (1995-02-01), None
patent: WO-95/15952 (1995-06-01), None
patent: WO-99/50250 (1999-10-01), None
patent: WO-00/12486 (2000-03-01), None
patent: WO-00/71536 (2000-11-01), None
patent: WO-02/083653 (2002-10-01), None
patent: WO-2002/083653 (2002-10-01), None
patent: WO-03/099771 (2003-12-01), None
patent: WO-2004/031232 (2004-04-01), None
patent: WO-2005/051366 (2005-06-01), None
patent: WO-2006/045066 (2006-04-01), None
patent: WO-2006/061415 (2006-06-01), None
patent: WO-2006/108487 (2006-10-01), None
patent: WO-2006/128129 (2006-11-01), None
patent: WO-2007/015923 (2007-02-01), None
patent: WO-2007/056151 (2007-05-01), None
patent: WO-2007/081630 (2007-07-01), None
patent: WO-2008/092199 (2008-08-01), None
U.S. Appl. No. 12/648,693, Singh et al.
International Search Report, PCT/US2008/11911, date of mailing Dec. 23, 2008.
Written Opinion, PCT/US2008/11911, date of mailing Dec. 23, 2008.
Okoh et al., “Pleckstrin Homology Domains of Tec Family Protein Kinases,”Biochemical and Biophysical Research Communications265:151-157 (1999).
Declue et al., “Epidermal growth factor receptor expression in neurofibromatosis type 1 related tumors and NF1 animal model,”Journal of Clinical Investigation105:1233-1241 (2000).
Zhang et al., “Targeting Cancer with Small Molecule Kinase Inhibitors,”Nature Rev. Cancer9:28-39 (2009).
Cohen et al., “Structural bioinformatics-based design of selective, irreversible inhibitors,”Science308:1318-1321 (2005).
Kwak et al., “Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib,”Proc. Natl. Acad. Sci. USA102:7665-7670 (2005).
Zhang et al., “Antitumor Activity of Epidermal Growth Factor Receptor-Related Protein Is Mediated by Inactivation of ErbB Receptors and Nuclear Factor-kB in Pancreatic Cancer,”Cancer Res66:1025-1032 (2006).
Lin et al., “New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors,”Breast Cancer Res6:204-210 (2004).
Andrulis et al., “Neu/ErbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer,”J Clin Oncol16:1340-9 (1998).
Fallon et al., “Constitutive activation of the neuregulin-1/erbB signaling pathway promotes the proliferation of a human peripheral neuroepithelioma cell line,”J Neuro Oncol66:273-84 (2004).
Stonecypher et al., “Activation of the neuregulin-1/ErbB signaling pathway promotes the proliferation of neoplastic Schwann cells in human malignant peripheral nerve sheath tumors,”Oncogene24:5589-5605 (2005).
Pelton et al., “Ruffling membrane, stress fiber, cell spreading and proliferation abnormalities in human Schwann cells,”Oncogene17:2195-2209 (1998).
Lajeunesse et al., “A systematic screen for dominant second-site modifiers of Merlin/NF2 phenotypes reveals an interaction with blistered/DSRF and scribbler,”Genetics158:667-79 (2001).
McClatchey et al., “Membrane organization and tumorigenesis—the NF2 tumor suppressor, Merlin,”Genes Dev19:2265-77 (2005).
Curto et al., “Contact-dependent inhibition of EGFR signaling by Nf2/Merlin,”J Cell Biol177:893-903 (2007).
Readinger et al., “Selective Targeting of ITK Blocks Multiple Steps of HIV Replication,”Proc. Natl. Acad. Sci. USA105: 6684-6689 (2008).
Frank, “STAT signaling in the pathogenesis and treatment of cancer,”Mol. Med. 5 :432-456 (1999).
Seidel et al., “Pharmaceutical intervention in the JAK/STAT signaling pathway,”Oncogene19 :2645-2656 (2000).
Malaviya et al., “Targeting Janus Kinase 3 in Mast Cells Prevents Immediate Hypersensitivity Reactions and Anaphylaxis,”J. Biol. Chem. 274 :27028-27038 (1999).
Kirken, “Targeting Jak3 for immune suppression and allograft acceptance,”Transplant. Proc. 33 :3268-3270 (2001).
Trieu et al., “A specific inhibitor of janus kinase-3 increases survival in a transgenic mouse model of amyotrophic lateral sclerosis,”Biochem. Biophys. Res. Commun. 267 :22-25 (2000).
Sudbeck et al., “Structure-based Design of Specific Inhibitors of Janus Kinase 3 as Apoptosis-inducing Antileukemic Agents,”Clin. Cancer Res. 5: 1569-1582 (1999).
Fry et al., “Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor,”Proc. Natl. Acad. Sci. USA95:12022-12027 (1998).
Zhang et al., “Discovery of EGFR selective 4,6-disubstituted pyrimidines from a combinatorial kinase-directed heterocycle library,”J. Am. Chem. Soc. 128:2182-2183 (2006).
Zhou et al., “Novel mutant-selective EGFR kinase inhibitors against EGFR T790M,”Nature462:1070-1074 (Dec. 2009).
Showalter et al, “Tyrosine kinase inhibitors. 16. 6,5,6-Tricyclic benzothieno[3,2-d]pyrimidines and Pyrimido[5,4-b] and —[4,5-b]indoles as potent inhibitors of the epidermal growth factor receptor tyrosine kinase,”J. Med. Chem. 42:5464-5474 (1999).
Singh et al, “Structure-based design of a potent, selective, and irreversible inhibitor of the catalytic domain of the erbB receptor subfamily of protein tyrosine kinases,”J. Med. Chem. 40:1130-1135 (1997).
International Search Report, PCT/US2010/31714, date of mailing Aug. 13, 2010.
Written Opinion, PCT/US2010/31714, date of mailing Aug. 13, 2010.
Li et al., “BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models,”Oncogene27:1-19 (2008).
Hur et al., “Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase,”Bioorg. Med. Chem. Lett.18:5916-5919 (2008).
Written Opinion, PCT/US2010/31714, date of mailing Aug. 13, 2010.
Li et al., “BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models,”Oncogene27:4702-4711 (2008).
Supplementary EP Search Report, EP08839939.9, date of mailing Feb. 4, 2011.

Affiliated with

Also associated with

Rating

4,6-disubstituted pyrimidines useful as kinase 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 4,6-disubstituted pyrimidines useful as kinase inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 4,6-disubstituted pyrimidines useful as kinase inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2780716