Methods of using indazole derivatives as JNK inhibitors

Details Methods of using indazole derivatives as JNK inhibitors Methods of using indazole derivatives as JNK inhibitors

2007-05-22

2007-05-22

Padmanabhan, Sreenivasan (Department: 1617)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

C514S381000, C514S383000

Reexamination Certificate

active

10673121

ABSTRACT:
Compounds having activity as selective inhibitors of JNK are disclosed. The compounds of this invention are indazole derivatives having the following structure:wherein R1, R2and A are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

REFERENCES:
patent: 3994890 (1976-11-01), Fujimura
patent: 4415569 (1983-11-01), Yasuo et al.
patent: 6162613 (2000-12-01), Su et al.
patent: 6531491 (2003-03-01), Kania et al.
patent: 6534524 (2003-03-01), Kania et al.
patent: 6555539 (2003-04-01), Reich et al.
patent: 2002/0161022 (2002-10-01), Reich et al.
patent: 12 66 763 (1968-04-01), None
patent: 0 494 774 (1992-07-01), None
patent: 0 518 805 (1992-12-01), None
patent: 1293557 (1970-09-01), None
patent: 2 345 486 (2000-07-01), None
patent: WO 98/43969 (1998-10-01), None
patent: WO 99/53927 (1999-10-01), None
patent: WO 01/12621 (2001-02-01), None
patent: WO 02/085396 (2002-10-01), None
Carter et al. Chemotherapy of Cancer, Second Edition, pp. 361-363, 365. 1981.
Aspenström et al., 1996, “Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome”, Curr. Biol. 6:70-75.
Chen et al., 1996, “Activation and inhibition of the AP-1 complex in human breast cancer cells”, Mol. Carcinogenesis 15:215-226.
Dong et al., 1998, “Defective T cell differentiation in the absence ofJnkl”, Science 282:2092-2095.
Faris et al., 1996, “Regulation of interleukin-2 transcription by inducible stabile expression of dominant negative and dominant active mitogen-activated protein kinase kinase kinase in Jurkat T cells”, J. Biol. Chem. 271:27366-27373.
Gum et al., 1997, “Regulation of 92 kDa type IV collagenase expression by thejunaminoterminal kinase- and the extracellular signal-regulated kinase- dependent signaling cascades”, Oncogene 14:1481-1493.
Han et al., 1999, “Jun N-terminal kinase in rheumatoid arthritis”, J. Pharmacol. Exp. Therap. 291:124-130.
Hibi et al., 1993, “Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun Activation domain”, Genes Dev. 7:2135-2148.
Ishizuka et al., 1997, “Mast cell tumor necrosis factor α production is regulated by MEK kinases”, Proc. Natl. Acad. Sci. USA 94:6358-6363.
Karin et al., 1997, “AP-1 function and regulation”, Curr. Opin. Cell. Biol. U9:240-246.
Lange-Carter et al., 1993, “A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf”, Science 260:315-319.
Li et al., 1996, “Blocked signal transduction to the ERK and JNK protein kinases in anergic CD4+T cells”, Science 271:1272-1276.
Li et al., 1996 “The Ras-JNK pathway is involved in shear-induced gene expression”, Mol. Cell. Biol. 16:5947-5954.
Lin et al., 1995, “Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2”, Science 268:286-290.
Manning and Mercurio, 1997, “Transcription inhibitors in inflammation”, Exp. Opin. Invest. Drugs 6:555-567.
Milne et al., 1995, “p53 is phosphorylatedin vitroandin vivoby an ultraviolet radiation-induced protein kinase characteristic of the c-Jun kinase, JNK1”, J. Biol. Chem. 270:5511-5518.
Mohit et al., 1995, “p493F12kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system”, Neuron 14:67-78.
Nishina et al., 1997, “Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes”, J. Exp. Med. 186:941-953.
Okamoto et al., 1997, “Selective activation of the JNK/AP-1 pathway in Fas-mediated apoptosis of rheumatoid arthritis synoviocytes”, Arthritis & Rheumatism 40:919-926.
Pombo et al., 1994, “The stress-activated protein kinases are major c-Jun amino-terminal kinases activated by ischemia and reperfusion”, J. Biol. Chem. 269:26546-26551.
Raitano et al., 1995, “TheBcr-Ablleukemia oncogene activates Jun kinase and requires Jun for transformation”, Proc.Natl. Acad. Sci. USA 92:11746-11750.
Sabapathy et al., 1999, “JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development”, Curr. Biol. 9:116-125.
Su et al., 1994, “JNK is involved in signal integration during costimulation of T lymphocytes”, Cell 77:727-736.
Swantek et al., 1997, “Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-α) translation: glucocorticoids inhibit TNF-α translation by blocking JNK/SAPK”, Mol. Cell. Biol. 17:6274-6282.
Szabo et al., 1996, “Altered cJUN expression: an early event in human lung carcinogenesis”, Cancer Res. 56:305-315.
Tournier et al., 1997, “Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase”, Proc. Natl. Acad. Sci. USA 94:7337-7342.
Whitmarsh and Davis, 1996, “Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways”, Mol. Med. 74:589-607.
Yan et al., 1994, “Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1”, Nature 372:798-800.
Yang et al., 1998, “Differentiation of CD4+T cells to Th1 cells requires MAP kinase JNK2”, Immunity 9:575-585.
Yin et al., 1997, “Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney”, J. Biol. Chem. 272:19943-19950.
Spiegelman et al., “Regulation of Adipocyte Gene Expression in Differentiation and Syndromes of Obesity/Diabetes”,J. of Biol. Chem. 268:6823-6826 (1993).
Hirosumi et al., “A central role for JNK in obesity and insulin resistance”,Letters to Nature 420:333-336 (2002).
Burgess et al., 1998, “Regulation of the c-junGene in p210 BCR-ABL Transformed Cells Corresponds With Activity of JNK, the c-junN-Terminal Kinase,”Blood 92(7):2450-2460.
Cripe et al., 2002, “Role for c-junN-terminal kinase in treatment-refractory acute myeloid leukemia (AML) signaling to multidrug-efflux and hyperproliferation,”Leukemia 16:799-812.
Hess et al., 2002, Survival signaling mediated by c-Jun NH2-terminal kinase in transformed B lymphoblasts,Nature Genetics 32:201-205.
Bost et al., 1999, “The Jun Kinase 2 Isoform Is Preferentially Required for Epidermal Growth Factor-Induced Transformation of Human A549 Lung Carcinoma Cells,”Molecular and Cellular Biology19(3):1938-1949.
Yang et al., 2003, “C-Jun NH2-terminal Kinase Mediates Proliferation and Tumor Growth of Human Prostate Carcinoma,”Clinincal Cancer Research 9:391-401.
Tsuuiki et al., 2003, “Constitutively Active Forms of c-Jun NH2-terminal Kinase Are Expressed in Primary Glial Tumors,”Cancer Research 63:250-255.
Potapova et al., 2000, “c-Jun N-terminal Kinase Is Essential for Growth of Human T98G Glioblastoma Cells,”J. Biol. Chem. 275(32):24767-24775.

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