Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2005-02-22
2005-02-22
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S250000, C514S359000, C514S362000, C514S366000, C514S375000, C514S388000, C514S394000, C544S101000, C544S345000, C548S126000, C548S151000, C548S218000, C548S256000, C548S257000, C548S260000, C548S302100
Reexamination Certificate
active
06858607
ABSTRACT:
The present invention is directed to substituted 4H-chromene and analogs thereof, represented by the general Formula I:or pharmaceutically acceptable salts or prodrugs thereof, wherein:wherein A, R1, R2, R5, X, Y, and Z, are defined herein and B is a fused thiazole, oxazole, 2-imino-imidazole, 2,1,3-thiadiazo-2-one, thiazol-2-one, oxazol-2-one, imidazol-2-thione, thiazol-2-thione, oxazol-2-thione, imidazoline, oxazoline, thiazoline, triazole, oxazine, oxazine-2,3-dione, or piperazine ring. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
REFERENCES:
patent: 3989816 (1976-11-01), Rajadhyaksha
patent: 4444762 (1984-04-01), Rajadhyaksha
patent: 5281619 (1994-01-01), Dell et al.
patent: 5284868 (1994-02-01), Dell et al.
patent: 5434160 (1995-07-01), Dell et al.
patent: 5514706 (1996-05-01), Ambler et al.
patent: 5571818 (1996-11-01), Williams
patent: 5574034 (1996-11-01), Williams
patent: 5576325 (1996-11-01), Williams
patent: 5624953 (1997-04-01), Ambler et al.
patent: 5637589 (1997-06-01), Lee et al.
patent: 5726204 (1998-03-01), Lee et al.
patent: 5847165 (1998-12-01), Lee et al.
patent: 6160010 (2000-12-01), Uckun et al.
patent: 6221900 (2001-04-01), Uckun et al.
patent: 6258824 (2001-07-01), Yang
patent: 6294575 (2001-09-01), Uckun et al.
patent: 6303652 (2001-10-01), Uckun et al.
patent: 6335429 (2002-01-01), Cai et al.
patent: 6365626 (2002-04-01), Uckun et al.
patent: 6388092 (2002-05-01), Yang
patent: 0 537 949 (1993-04-01), None
patent: 0 599 514 (1994-06-01), None
patent: 0 618 206 (1994-10-01), None
patent: 0 619 314 (1994-10-01), None
patent: WO 9824427 (1998-06-01), None
patent: WO 9954286 (1999-10-01), None
patent: WO 0134591 (2001-05-01), None
A1-Mousawi, S.M., et al., “Synthesis of New Condensed 2-Amino-4H-Pyran-3-Carbonitriles and of 2-Aminoquinoline-3-Carbonitriles,”Organic Preparations and Procedures Int.31:305-313, Organic Preparations and Procedures Inc. (1999).
Batteux, F., et al., “Gene Therapy of Experimental Autoimmune Thyroiditis by In Vivo Administration of Plasmid DNA Coding for Fas Ligand,”J. Immunol.162:603-608, The American Association of Immunologists (1999).
Birch, K.A., et al., “LY290181, an Inhibitor of Diabetes-Induced Vascular Dysfunction, Blocks Protein Kinase C-Stimulated Transcriptional Activation Through Inhibition of Transcription Factor Binding to a Phorbol Response Element,”Diabetes45:642-650, American Diabetes Association (1996).
Bloxham, J., et al., “Preparation of Some New Benzylidenemalononitriles by an SNAr Reaction: Application to Naphtho[1,2-b] pyran Synthesis.”Heterocycles38:399-408, The Japan Institute of Heterocyclic Chemistry (1994).
Boirivant, M., et al., “Lamina Propria T Cells in Crohn's Disease and Other Gastrointestinal Inflammation Show Defective CD2 Pathway-Induced Apoptosis,”Gastroenterology116:557-565, The American Gastroenterological Association (1999).
Chandrasekhar, S., et al., “Indentification of a Novel Chemical Series That Blocks Interleukin-1-Stimulated Metalloprotease Activity in Chrondrocytes,”J. Pharmacol. Exp. Ther.273:1519-1528, The American Society for Pharmacology and Experimental Therapeutics (1995).
Sharanin, Y.A., and Klokol, G.V., “Synthesis of 2-amino-4H-chromenes,” Chemical Abstracts, vol. 99, No. 27, Abstract No. 212393z, American Chemical Society (1983).
Wiernicki, T.R., et al., “Inhibition of vascular smooth muscle cell proliferation and arterial intimal thickening by a novel antiproliferative naphthopyran,” Chemical Abstracts, vol. 125, No. 21, Abstract No. 265467p, American Chemical Society (1996).
Coven, T.R., et al., “PUVA-induced lymphocyte apoptosis: Mechanism of action in psoriasis,”Photodermatol. Photoimmunol. Photomed.15:22-27, Munksgaard (1999).
Elagamey, A.G.A., et al., “Nitriles in Heterocyclic Synthesis: Novel Syntheses of Benzo[b] pyrans, Naphtho [1,2-b] pyrans, Naphtho [2,1-b] pyrans, Pyrano [3,2-h] quinolines and Pyrano [3,2-c] quinolines,”Collection Czechoslovak. Chem. Commun.53:1534-1538, Institute of Organic Chemistry and Biochemistry (1988).
Friesen, C., et al., “Involvement of the CD95 (APO-1/Fas) receptor/ligand system in drug-induced apoptosis in leukemia cells,”Nat. Med.2:574-577, Nature Publishing Co. (1996).
Greenwald, R.B., “Drug Delivery Systems Employing 1,4—or 1, 6-Elimination: Poly (ethylene glycol) Prodrugs of Amine-Containing Compounds,”J. Med. Chem.42:3657-3667, American Chemical Society (1999).
Heenen, M., et al., “Methotrexate induces apoptotic cell death in human keratinocytes,”Arch. Dermatol. Res.290:240-245, Springer-Verlag (1998).
Infante, A.J., et al., “The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis,”J. Pediatr.133:629-633, Mosby, Inc. (1998).
International Search Report for International Application No. PCT/US 02/15398, mailed Oct. 25, 2002.
Klokol, G.V., et al., “Cyclization of Nitriles. XXIII. Addition of Active Phenols to Electron-Deficient Ethylenes, Accompanied by Cyclization to 2-Amino-4H-benzo[b]pyrans. Crystal Structure of 2-Amino-4-(2-Fluorophenyl)-3-Ethoxycarbonyl-4H-Naphtho[2,1-b]pyran”J. Org. Chem. USSR23:369-377, Plenum Publishing Corporation (1987).
Leu, Y.-L., et al., “Design and Synthesis of Water-Soluble Glucuronide Derivatives of Camptothecin for Cancer Prodrug Monotherapy and Antibody-Directed Enzyme Prodrug Therapy (ADEPT),”J. Med. Chem.42:3623-3628, American Chemical Society (1999).
López-Hoyos, M., et al., “Regulation of B cell apoptosis by Bcl-2 and Bcl-XLand its role in the development of autoimmune diseases (Review),”Int. J. Mol. Med.1:475-483, D.A. Spandidos (1998).
Los, M., et al., “Cross-Resistance of CD95- and Drug-Induced Apoptosis as a Consequence of Deficient Activation of Caspases (ICE/Ced-3 Proteases),”Blood90:3118-3129, The American Society of Hematology (1997).
McCarty, M.F., “Polyphenol-mediated inhibition of AP-1 transactivating activity may slow cancer growth by impeding angiogenesis and tumor invasiveness.”Med. Hypotheses50:511-514, Harcourt Brace & Co. Ltd. (1998).
O'Reilly, L.A., and Strasser, A., “Apoptosis and autoimmune disease,”Inflamm. Res.48:5-21, Birkhauser Verlag (1999).
Ohsako, S., and Elkon, K.B., “Apoptosis in the effector phase of autoimmune diabetes, multiple sclerosis and thyroiditis,”Cell Death Differ.6:13-21, Stockton Press (1999).
Orrenius, S., “Apoptosis: molecular mechanisms and implications for human disease,”J. Int. Med.237:529-536, Blackwell Science Ltd. (1995).
Ozawa, M., et al., “312-nanometer Ultraviolet B Light (Narrow-Band UVB) Induces Apoptosis of T Cells within Psoriatic Lesions,”J. Exp. Med.189:711-718, The Rockefeller University Press (1999).
Panda, D., et al., “Suppression of Microtubule Dynamics by LY2910181, a Potential Mechanism for Its Antiproliferative Action,”J. Biol. Chem.272:7681-7687, The American Society for Biochemistry and Molecular Biology, Inc. (1997).
Paull, K.D., et al., “Identification of Novel Antimitotic Agents Acting at the Tubulin Level by Computer-assisted Evaluation of Differential Cytotoxicity Data,”Cancer Res.52:3892-3900, American Association for Cancer Research, Inc. (1992).
Cai et al., Pending Non-Provisional U.S. Appl. No. 09/705,840, filed Nov. 6, 2000 (not published).
Cai et al., Pending Non-Provisional U.S. Appl. No. 10/146,138, filed May 16, 2002 (not published).
Cai et al., Pending Non-Provisional U.S. Appl. No. 10/146,136, filed May 16, 2002 (not published).
Radwan, S.M., et al., “S
Attardo Giorgio
Cai Sui Xiong
Storer Richard
Xu Lifen
Cytovia, Inc.
Raymond Richard L.
Sterne Kessler Goldstein & Fox P.L.L.C.
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