4,6-disubstitued pyrimidines useful as kinase inhibitors

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

2011-07-19

2011-07-19

Wilson, James O (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitrogen attached directly or indirectly to the purine ring...

C544S111000, C544S359000, C546S119000, C546S121000, C546S210000, C546S290000, C548S165000, C548S205000, C548S217000, C548S518000, C549S408000, C549S548000

Reexamination Certificate

active

07982036

ABSTRACT:
The present invention provides compounds of formula Iwherein Ring A, Ring B, m, Rx, Ry, W and R1are as defined herein, pharmaceutically acceptable salts and compositions thereof, and methods of using the same.

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: 2004/0023895 (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: 2009/0181987 (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: 07041461 (1995-02-01), None
patent: WO-95/15952 (1995-06-01), None
patent: WO-99/50250 (1999-10-01), None
patent: WO-00/71536 (2000-11-01), None
patent: WO-02/083653 (2002-10-01), None
patent: WO-2004/031232 (2004-04-01), 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-2007/056151 (2007-05-01), None
patent: WO-2007/081630 (2007-07-01), None
patent: WO-2008/092199 (2008-08-01), None
U.S. Appl. No. 12/426,495, Singh et al.
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,”Oncogene27:4702-4711 (2008).
Hur et al., “Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase,”Bioorg. Med. Chem. Lett. 18:5916-5919 (2008).

Affiliated with

Also associated with

Rating

4,6-disubstitued 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-disubstitued 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-disubstitued pyrimidines useful as kinase inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2708645