Compositions and methods for inhibiting TGF-β

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C546S163000, C546S162000

Reexamination Certificate

active

10869321

ABSTRACT:
The present invention provides compounds of the formula:and pharmaceutically acceptable isomers, salts, hydrates, solvates, and prodrug derivatives thereof, wherein R1, R6, R7, R8, Pg, and n are those defined herein. The present invention also provides pharmaceutical compositions comprising the same and methods for using the same. In particular, compounds of Formula I are useful in modulating TGF-β activity.

REFERENCES:
patent: 4739762 (1988-04-01), Palmaz
patent: 5195984 (1993-03-01), Schatz
patent: 5780482 (1998-07-01), Armitage et al.
patent: 6638945 (2003-10-01), Gibson
patent: 6809106 (2004-10-01), Gibson
patent: 2005/0009815 (2005-01-01), DeVita et al.
patent: 0 705 260 (1999-03-01), None
patent: WO 02/079165 (2002-10-01), None
Roberts and Sporn, “The Transforming Growth Factor-βs” in:Peptide Growth Factors and Their Receptors. I. Handbook of Experimental Pharmacology, Springer-Verlag, Berlin, 1990, vol. 95, No. 1, pp. 419-472.
Berge et al., “Pharmaceutical Salts,”J. of Pharmaceutical Science, 1977, vol. 66, pp. 1-19.
Bundgaard, H. (Ed.)Design of Prodrugs, pp. 7-9 and 21-24, Elsevier, Amsterdam, 1985.
Derynck, R. et al., “Nomenclature: Vertebrate mediators of TGFβ Family Signals,”Cell, 1996, vol. 87, p. 173.
Derynck R. and Y. Zhang, “Intracellular signaling: The Mad way to do it,”Curr. Biol., 1996, vol. 6, pp. 1226-1229.
Derynck, R., “TGF-β-receptor-mediated signaling,”Trends Biochem. Sci., 1994, vol. 19, pp. 548-553.
Dijke, P. et al., “Signaling via hetero-oligomeric complexes of type I and type II serine/theroine kinase receptors,”Curr. Opin. Cell Biol., 1996, vol. 8, pp. 139-145.
Eppert, K. et al., “MADR2 maps to 18q21 and encodes a TGFβ-regulated MAD-related protein that is functionally mutated in colorectal carcinoma,”Cell, 1996, vol. 86, pp. 543-552.
Grainger, D.J. and J.C. Matcliffe, “A pivotal role for TGF-β in atherogenesis?”Bio. Rev. Cambridge Phil. Soc., 1995, vol. 70, pp. 571-596.
Hahn, S.A. et al., “DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1”Science, 1996, vol. 271, pp. 350-353.
Hoodless, P.A. et al., “MADR1, a MAD-related protein that functions in BMP2 Signaling Pathways,”Cell, 1996, vol. 85, pp. 489-500.
Hoosein, N.M. et al., “Differential sensitivity of subclasses of human colon carcinoma cell lines to the growth inhibitory effects of transforming growth factor-β1,”Exp. Cell. Res., 1989, vol. 181, pp. 442-453.
Kretzschmar, M. et al., “The TGF-β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase,”Genes Dev., 1997, vol. 11, pp. 984-995.
Lagna, G. et al., “Partnership between DPC4 and SMAD proteins in TGF-β signaling pathways,”Nature, 1996, vol. 383, pp. 832-836.
Lin H.Y. and H.F. Lodish, “Receptors for the TGF-β superfamily: multiple polypeptides and serine/threonine kinases,”Trends Cell Biol., 1993, vol. 3, No. 1; pp. 14-19.
Liu, F. et al., “A human Mad protein acting as a BMP-regulated transcriptional activator,”Nature, 1996, vol. 381, pp. 620-623.
Massagué, J. and F. Weis-Garcia, “Serine/theronine kinase receptors: Mediators of transforming growth factor beta family signals,”Cancer Surv., 1996, vol. 27, pp. 41-64.
Massagué, J., “TGF-β signaling: Receptors, transducers, and Mad proteins,”Cell, 1996, vol. 85, pp. 947-950.
Meersseman, G. et al., “The C-terminal domain of Mad-like signal tranducers is sufficient for biological activity in theXenophusembryo and transcriptional activation,”Mech. Dev., 1997, vol. 61, pp. 127-140.
Metcalfe, J. and D.J. Grainger, “TGF-β: Implications for human vascular disease,”J. Human Hypertens., 1995, vol. 9, pp. 679.
Murthy, U. et al., “Expression of TGF-α/EGF and TGF-β receptors in human colon carcinoma cell lines,”Int'l J. Cancer, 1989, vol. 44, pp. 110-115.
Nakao, A. et al., “Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice,”J. Clin. Inv., 1999, vol. 104, pp. 5-11.
Newfeld, S.J. et al., “Mothers against dppencodes a conserved cytoplasmic protein required in DPP/TGF-β responsive cells,”Development, 1996, vol. 122, pp. 2099-2108.
Riggins, G. et al., “Mad-related genes in the human,”Nature Genet., 1996, vol. 13, pp. 347-349.
Sato, M. et al., “Transforming growth factor-β1proliferated vascular smooth muscle cells from spontaneously hypertensive rats,”Am. J. Hypertens., 1995, vol. 8, pp. 160-166.
Savage, C. et al., “Caenorhabditis elegansgenessma-2, sma-3, andsma-4define a conserved family of transforming growth factor β components,”Proc. Natl. Acad. Sci. USA, 1996, vol. 93, pp. 790-794.
Schulick, A.H. et al., “Overexpression of transforming growth factor β1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia,”Proc. Natl. Acad. Sci. USA, 1988, vol. 95, pp. 6983-6988.
Sekelsky, J.J. et al., “Genetic characterization and cloning ofMothers against dpp, a gene required fordecapentaplegicfunction inDrosophila melanogaster,” Genetics, 1995, vol. 139, pp. 1347-1358.
Shull, M.M. et al., “Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease,”Nature, 1992, vol. 359, pp. 693-699.
Silverman, R.B.,The Organic Chemistry of Drug Design and Drug Action, pp. 352-401, Academic Press, San Diego, CA, 1992.
Wahl, S.M. et al., “Inflammatory and immunomodulatory roles of TGF-β,”Immunol. Today, 1989, vol. 10, pp. 258-261.
Welch, D.R. et al., Transforming growth factor β stimulates mammary adenocarcinoma cell invasion and metastatic potential,Proc. Natl. Acad. Sci. USA., 1990, vol. 87, pp. 7678-7682.
Wiersdorf, V. et al., “Mad acts downstream of Dpp receptors, revealing a differential requirement fordppsignaling in initiation and propagation of morphogenesis in theDrosophilaeye,”Development, 1996, vol. 122, pp. 2153-2163.
Wieser, R. et al., “GS domain mutations that constitutively activate TβR-I, the downstream signaling component in the TGF-β receptor complex,”EMBO J., 1995, 14, pp. 2199-2208.
Wrana, J.L. et al., “Mechanism of activation of the TGF-β receptor,”Nature, 1994, vol. 370, pp. 341-347.
Wrana, J.L. and L. Attisano, “MAD-related proteins in TGF-β signaling,”Trends Genet., 1996, vol. 12, pp. 493-496.
Wu, R.Y. et al., “Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4,”Mol. Cell. Biol., 1997, vol. 17, pp. 2521-2528.
Ziyadeh, F.N. et al., “Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-β antibody indb/dbdiabetic mice,”Proc. Natl. Acad. Sci., 2000, vol. 97, pp. 8015-8020.

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