Isoxazoline compounds having MIF antagonist activity

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C548S240000

Reexamination Certificate

active

07662843

ABSTRACT:
Methods of use and pharmaceutical compositions for a genus of low molecular weight compounds comprising optionally substituted isoxazoline ring systems that act as inhibitors of MIF (macrophage migration inhibitory factor) are disclosed. Specifically, the compounds are useful for treating a variety of diseases involving inflammatory activity or pro-inflammatory cytokine responses, such as autoimmune diseases (including rheumatiod arthritis, insulin-dependent diabetes, multiple sclerosis, graft versus host disease, lupus syndromes), asthma, arthritis, ARDS, psoriasis, interleukin-2 toxicity, proliferative vascular disease, and various forms of sepsis and septic shock, and other conditions characterized by underlying MIF responses including, for instance, tumor growth and neovascularization (angiogenesis).

REFERENCES:
patent: 4933464 (1990-06-01), Markofsky
patent: 5716967 (1998-02-01), Kleinman
patent: 5849736 (1998-12-01), Wityak et al.
patent: 6114367 (2000-09-01), Cohan et al.
patent: 6599903 (2003-07-01), de Lassauniere et al.
patent: 6630461 (2003-10-01), de Lassauniere et al.
Cvetkovic, I. and Stosic-Grujicic “Neutralization of mcrophage migration inhibitory factor-novel approach for the treatment of immunoinflammatory disorders” 2006, International Immunopharmocology, vol. 6, pp. 1527-1534.
Swope, et al., “Macrophage Migration Inhibitory Factor: Cytokine, Hormone, or Enzyme?”, Rev. Physiol. Bicohem. Pharmacol., 139, 1-32 (1999).
Metz, et al., “Role of Macrophage Migration Inhibitory Factor in the Regulation of the Immune Response”, Adv. Immunol., 66, 197-223 (1997).
Bucala, “MIF Rediscovered: Cytokine, Pitutary Hormone, and Glucocorticoid-Induced Regulator of the Immune Response”, FASEB J., 14, 1607-1613 (1996).
George, et al., “In vitro Cell Migration as a Model for Delayed Hypersensitivity”, Proc. Soc. Exp. Biol. Med., 111, 514-521 (1962).
Weiser, et al., “Studies on Human Inhibitory Factor: Characterization of Three Molecular Species”, J. Immunol., 126, 5, 1958-1962 (1981).
Bloom, et al., “Mechanism of a Reaction in Vitro Associated with Delayed-Type Hypersensitivity”, Science, 153, 80-82 (1966).
David, “Delayed Hypersensitivity in Vitro: Its Mediation by Cell-Free Substances Formed by Lymphoid Cell-Antigen Interaction”, Proc. Natl. Acad. Sci. USA, 56, 72-77 (1966).
Nathan, et al., “Characterization of a Lymphocyte Factor Which Alters Macrophage Functions”, J. Exp. Med., 137, 275-288 (1973).
Nathan, et al., “Alterations of Macrophage Functions by Mediators from Lymphocytes”, J. Exp. Med., 133, 1356-1376 (1971).
Churchill, et al., “Macrophages Activated as Suspension Cultures with Lymphocyte Mediators Devoid of Antigen Become Cytotoxic for Tumor Cells”, J. Immunol., 115, 8, 781-785 (1975).
McInnes, et al., “Interleukin 4 Induces Cultured Monocytes/Macrophages to Form Giant Multinucleated Cells”, J. Exp. Med., 167, 598-611 (1988).
Thurman, et al., “MIF-Like Activity of Natural and Recombinant Human Interferon-γ and Their Neutralization by Monoclonal Antibody”, J. Immunol., 134, 1, 305-309 (1985).
Weiser, et al., “Molecular Cloning of a cDNA Encoding a Human Macrophage Migration Inhibitory Factor”, Proc. Natl. Acad. Sci. USA, 86, 7522-7526 (1989).
Weiser, et al., “Human Recombinant Migration Inhibitory Factor Activates Human Macrophages to KillLeishmania donovani”, J. Immunol., 147, 6, 2006-2011(1991).
Pozzi, et al., “Human Recombinant Migration Inhibitory Factor Activates Human Macrophages to Kill Tumor Cells”, Cellular Immunol., 145, 372-379 (1992).
Weiser, et al., “Recombinant Human Migration Inhibitory Factor Has Adjuvant Activity”, Proc. Natl. Acad. Sci. USA, 89, 8049-8052 (1992).
Cunha, et al., “Recombinant Migration Inhibitory Factor Induces Nitric Oxide Synthase in Murine Macrophages”, J. Immunol., 150, 5, 1908-1912 (1993).
Rice, et al., “Macrophage Migration Inhibitory Factor (MIF): A Critical Upstream Regulator of Acute and Chronic Inflammatory Responses”, Chapter 24, Annual Reports in Medicinal Chemistry, 33, 243-252 (1998).
Donnelly, et al., “Macrophage Migration Inhibitory Factor: A Regulator of Glucocorticoid Activity with a Critical Role in Inflammatory Disease”, Molecular Medicine Today, 3, 502-507 (1997).
Bacher, et al., “An Essential Regulatory Role for Macrophage Migration Inhibitory Factor in T-Cell Activation”, Proc. Natl. Acad. Sci. USA, 93, 7849-7854 (1996).
Mikayama, et al., “Molecular Cloning and Functional Expression of a cDNA Encoding Glycosylation-Inhibiting Factor”, Proc. Natl. Acad. Sci. USA, 90, 10056-10060 (1993).
Hudson, et al., “A Proinflammatory Cytokine Inhibits p53 Tumor Suppressor Activity”, J. Exp. Med., 190, 10, 1375-1382 (1999).
Sakaue, et al., “Regulation of Macrophage Migration Inhibitory Factor (MIF) Expression by Glucose and Insulin in Adipocytes In Vitro”, Mol. Med., 5, 361-371 (1999).
Chesney, et al., “An Essential Role for Macrophage Migration Inhibitory Factor (MIF) in Angiogenesis and the Growth of a Murine Lymphoma”, Mol. Med., 5, 181-191 (1999).
Shimizu, et al., “High Expression of Macrophage Migration Inhibitory Factor in Human Melanoma Cells and Its Role in Tumor Cell Growth and Angiogenesis”, Biochem. and Biophys. Res. Commun. 264, 751-758 (1999).
Rosengren, et al., “The Immunoregulatory Mediator Macrophage Migration Inhibitory Factor (MIF) Catalyzes a Tautomerization Reaction”, Mol. Med., 2, 1, 143-149 (1996).
Bendrat, et al., “Biochemical and Mutational Investigations of the Enzymatic Activity of Macrophage Migration Inhibitory Factor”, Biochemistry, 36, 15356-15362 (1997).
Rosengren, et al., “The Macrophage Migration Inhibitory Factor MIF is a Phenylpyruvate Tautomerase”, FEBS Letters, 417, 85-88 (1997).
Matsunaga, et al., “Enzyme Activity of Macrophage Migration Inhibitory Factor Toward Oxidized Catecholamines”, J. Biol. Chem., 274, 6, 3268-3271 (1999).
Lolis, et al., “Crystal Structure of Macrophage Migration Inhibitory Factor (MIF), a Glucocorticoid-Induced Regulator of Cytokine Production, Reveals a Unique Architecture”, Proc. Ass. Am. Phys., 108, 6, 415-419 (1996).
Swope, et al., “Direct Link Between Cytokine Activity and a Catalytic Site for Macrophage Migration Inhibitory Factor”, EMBO, 17, 13, 3534-3541 (1998).
Sugimoto, et al., “Crystal Structure of Humanimg id="CUSTOM-CHARACTER-00001" he="3.13mm" wi="2.46mm" file="US07662843-20100216-P00001.TIF" alt="custom character" img-content="character" img-format="tif" ?-Dopachrome Tautomerase, a Homologue of Macrophage Migration Inhibitory Factor, at 1.54 Å Resolution”, Biochemistry, 38, 3268-3279 (1999).
Lubetsky, et al., “Pro-1 of Macrophage Migration Inhibitory Factor Functions as a Catalytic Base in the Phenylpyruvate Tautomerase Activity”, Biochemistry, 38, 7346-7354 (1999).
Taylor, et al., “Crystal Structure of Macrophage Migration Inhibitory Factor Complexed with (E)-2-Fluoro-p-hydroxycinnamae at 1.8 Å Resolution: Implications for Enzymatic Catalysis and Inhibition”, Biochemistry, 38, 7444-7452 (1999).
Hermanowski-Vosatka, et al., “Enzymatically Inactive Macrophage Migration Inhibitory Factor Inhibits Monocyte Chemotaxis and Randome Migration”, Biochemistry, 38, 12841-12849 (1999).
Bernhagen, et al., “MIF is a Pituitary-Derived Cytokine that Potentiates Lethal Endotoxaemia”, Nature, 365, 756-759 (1993).
Kobayashi, et al., “Prevention of Lethal Acute Hepatic Failure by Antimacrophage Migration Inhibitory Factor Antibody in Mice Treated with Bacille Calmette-Guerin and Lipopolysaccharide”, Hepatology, 29, 1752-1759 (1999).
Calandra, et al., “Macrophage Migration Inhibitory Factor is a Critical Mediator of the

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