Isoxazoline compounds having MIF antagonist activity

Details Isoxazoline compounds having MIF antagonist activity Isoxazoline compounds having MIF antagonist activity

2011-04-19

2011-04-19

Padmanabhan, Sreeni (Department: 1627)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

C514S471000, C548S240000

Reexamination Certificate

active

07928130

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 rheumatoid 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), Chabrier De Lassauniere et al.
patent: 6630461 (2003-10-01), Chabrier De Lassauniere et al.
patent: 2003/0078420 (2003-04-01), Chabrier De Lassauniere et al.
patent: 2004/0204464 (2004-10-01), Al-Abed
patent: 27876 02 (1998-08-01), None
patent: WO9858934 (1998-12-01), None
Eichenger et al. “A novel base promoted reaction of methyl 2-isoxazoline-5-acetates to 5-(2-oxoethyl)-3-isoxazolidinones” Synthetic Communications, 1998, vol. 28(13), pp. 2457-2466.
Curuzu, et al., “Reaction of 4-Aroly-2 (3H)-Dihydrofuranones with Hydroxylamine Hydrochloride. Synthesis and Pharmacological Study of a Series of 3-Ary1-4, 5-Dihydro-4-Isoxazoleacetic Acids”, Collect. Czech. Chem. Commun., 56, 2494-2499 (1991).
Wityak, et al., “Discovery of Potent Isoxazoline Glycoprotein IIb/IIIa Receptor Antagonists”, J. Med. Chem., 40, 50-60 (1997).
Eichinger, et al., “A Convenient Synthesis of 3- and 3, 4-Substituted 4,5-Dihydroisoxazole-5-Acetic Acids”, Synth. Commun., 27, 16, 2733-2742 (1997).
Eichinger, et al., “A Novel Base Promoted Reaction of Methyl 2-Isoxazoline-5-Acetates to 5-(2-Oxoethyl)-3-Isoxazolidinones”, Synth. Commun., 28, 13, 2457-2466 (1998).
Kleinman, et al., “Striking Effect on Hydroxamic Acid Substitution on the Phosphodiestrase Type 4 (PDE4) and TNF. alpha. Inhibitory Activity of Two Series of Rolipram Analogues: Implications for New Active Site Model of PDE4”, J. Med. Chem., 41, 266-270 (1998).
Donnelly, et al., “Regulatory Role for Macrophage Migration Inhibitory Factor in Acute Respiratory Distress Syndrome”, Nat. Med. 3, 3, 320-323 (1997).
Leech, et al., “Involvement of Macrophage Migration Inhibitory Factor in the Evolution of Rat Adjuvant Arthritis”, Arthritis & Rheum., 41, 5, 910-917 (1998).
Onodera, et al., “High Expression of Macrophage Migration Inhibitory Factor in the Synovial Tissues of Rheumatoid Joints”, Cytokine, 11, 2, 163-167 (1999).
Mikulowska, et al., “Macrophage Migration Inhibitory Factor is Involved in the Pathogenesis of Collagen Type II-Induced Arthritis in Mice”, J. Immunol. 158, 5514-5517 (1997).
Shimizu, et al., “Identification of Macrophage Migration Inhibitory Factor (MIF) in Human Skin and Its Immunohistochemical Localization”, FEBS Lett., 381, 199-202 (1996).
Takahashi, et al., “Involvement of Macrophage Migration Inhibitory Factor (MIF) in the Mechanism of Tumor Cell Growth”, Mol. Med., 4, 707-714 (1998).
Bozza, et al., “Targeted Disruption of Migration Inhibitory Factor Gene Reveals Its Critical Role in Sepsis”, J. Exp. Med., 189, 2, 341-346 (1999).
Fingl, et al., “Introduction: General Principles”, The Pharmacological Basis of Therapeutics, Chapter 1, 1-46 (1975).
Xue, et al., “Discovery of an Orally Active Series of Isoxazoline Glycoprotein IIb/IIIa Antagonists”, J. Med. Chem., 40, 2064-2084 (1997).
Bernhagan, et al., “Purification, Biocactivity, and Secondary Structure Analysis of Mouse and Human Macrophage Migration Inhibitory Factor (MIF)”, Biochemistry, 33, 14144-14155 (1994).
Baraldi, P.G., et al., Nitrile Oxide [3+2] Cycloaddition: Application to the Synthesis of 6-Substituted 3(2H)-Pyridazinones and 6-Substituted 4,5-Dihydro-4-hydroxy-3(2H)-pyridazinones; 1994; Synthesis, pp. 1158-1162.
STN CAPlus entry for Registry No. 218944-54-8.
Lubetsky, Jodi B., et al., The Tautomerase Active Site of Macrophage Migration Inhibitory Factor Is a Potential Target for Discovery of Novel Anti-inflammatory Agents; May 7, 2002; The Journal of Biological Chemistry; vol. 277, No. 288, pp. 24976-24982.
Eichinger, Karl, et al., A Convenient Synthesis of 3-and 3,4-Substituted 4,5-Dihydroisoxazole-5-Acetic Acids; 1997 Synthetic Communications; 27(16), pp. 2733-2742.
Bundgaard, Hans, Design of prodrugs: Bioreversible derivatives for various functional groups and chemical entities; 1984; Elsevier Science Publishers B.V. Biomedical Division; pp. 1.
Kanemasa, Shuji, et al., Synthesis of Substituted Pyridines by a Cycloaddition Route Using Nitrite Oxides and Homoallyl Alcohols; 1991; Bull. Chem. Soc. Japan, 64, pp. 375-380.
ACS STN Registry: 139475-15-3, see the structure of the compound, 5-Isoxazoleacetic acid, 4,5-dihydro-3,4-diphenyl-,methyl ester; pp. 1-2.
ACS STN Registry: 134370-34-6, see structure of the compound, pp. 1.
Swope et al., Macrophage Migration Inhibitory Factor: Cytokine, Hormone, or Enzyme?; Rev. Physiol. Biochem. Pharmacol., 139, pp. 1-32 (1999).
Metz et al., Role of Macrophage Migration Inhibitory Factor in the Regulation of the Immune Response; Advances in Immunology; vol. 66, pp. 197-223 (1997).
Bucala, Richard, 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 Migration Inhibitory Factor Characterization of Three Molecular Species; Journal of Immunol., vol. 126 No. 5, pp. 1958-1962 (May 1981).
Bloom, Barry R., et al. Mechanism of a Reaction in Vitro Associated with Delayed-Typed Hypersensitivity Science vol. 153, 80-82 (1966).
David, John R., Delayed Hypersensitivity in Vitro: Its Mediation by Cell-Free Substances Formed by Lymphoid Cell-Antigen Interaction; Proc. Natl. Acad. Sci., USA, vol. 56, pp. 72-77 (1966).
Nathan et al. Characterization of a Lymphocyte Factor Which Alters Macrophage Functions, Journal of Experimental Medicine, vol. 137, pp. 275-288 (1973).
Nathan et al., Alterations of Macrophage Functions by Mediators from Lymphocytes; Journal of Experimental Medicine, vol. 133, pp. 1356-1376 (1971).
Churchill Hallowell W., et al., Macrophages Activated as Suspension Cultures with Lymphocyte Mediators Devoid of Antigen Become Cytotoxic for Tumor Cells, J.Immunol. vol. 115, No. 8, pp. 781-785 (1975).
McInnes A., et al., Interleukin 4 Induces Cultured Monocytes/Macrophages to form Giant Multinucleated Cells, Journal of Experimental Medicine, vol. 167, 598-611 (1988).
Thurman, Gary B., et al., MIF-Like Activity of Natural and Recombinant Human Interferon-gamma and Their Neutralization by Monoclonal Antibody, The Journal of Immunology, vol. 134, No. 1, 305-309 (1985).
Weiser, W.Y., et al., Molecular Cloning of a cDNA Encoding a Human Macrophage Migration Inhibitory Factor, Proc. Natl. Acad. Sci. USA, vol. 86, pp. 7522-7526 (1989).
Weiser, W.Y., et al., Human Recombinant Migration Inhibitory Factor Activates Human Macrophages to Kill Leishmania donovani, The Journal of Immunology, vol. 147, No. 6, 2006-2011 (1991).
Pozzi, L., et al., Human Recombinant Migration Inhibitory Factor Activates Human Macrophages to Kill Tumor Cells, Cellular Immunology, vol. 145, pp. 372-379 (1992).
Weiser, W.Y., et al., Recombinant Human Migration Inihibitory Factor has Adjuvant Activity, Proc. Natl. Acad. Sci. USA, vol. 89, pp. 8049-8052 (1992).
Cunha, F.Q., et al., Recombinant Migration Inhibi

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