Synthesis and biological activities of new tricyclic- bis...

Details Synthesis and biological activities of new tricyclic- bis... Synthesis and biological activities of new tricyclic- bis...

2010-05-10

2011-11-29

Loewe, Sun Jae (Department: 1622)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Silicon containing doai

C514S400000, C514S428000, C514S510000, C514S564000, C514S662000

Reexamination Certificate

active

08067394

ABSTRACT:
This invention describes novel tricyclic-bis-enone derivatives (TBEs), such as TBE-31, TBE-34, TBE-45 and water-soluble TBEs. The methods of preparing these compounds are also disclosed. The inventors demonstrate the ability of these new TBEs to inhibit proliferation of human myeloma cells, inhibit the induction of iNOS in cells stimulated with interferon-γ, induce heme oxygenase-1 (HO-1), induce CD11b expression—a leukemia differentiation marker, inhibit proliferation of leukemia cells, induce apoptosis in human lung cancer, and induce apoptosis in other cancerous cells. The TBEs of this invention are expected to be useful agents for the treatment and prevention of many diseases, including cancer, neurological disorders, inflammation, and pathologies involving oxidative stress.

REFERENCES:
patent: 4395423 (1983-07-01), Neumann
patent: 4808614 (1989-02-01), Hertel
patent: 5013649 (1991-05-01), Wang et al.
patent: 5064823 (1991-11-01), Lee et al.
patent: 5401838 (1995-03-01), Chou
patent: 5426183 (1995-06-01), Kjell
patent: 5464826 (1995-11-01), Grindey et al.
patent: 5521294 (1996-05-01), Wildfeuer
patent: 5597124 (1997-01-01), Kessel et al.
patent: 5603958 (1997-02-01), Morein et al.
patent: 5606048 (1997-02-01), Chou et al.
patent: 5972703 (1999-10-01), Long et al.
patent: 6025395 (2000-02-01), Breitner et al.
patent: 6303569 (2001-10-01), Greenwald et al.
patent: 6326507 (2001-12-01), Gribble et al.
patent: 6485756 (2002-11-01), Aust et al.
patent: 6974801 (2005-12-01), Honda et al.
patent: 7176237 (2007-02-01), Honda et al.
patent: 7265096 (2007-09-01), Gallop et al.
patent: 7288568 (2007-10-01), Gribble et al.
patent: 7435755 (2008-10-01), Konopleva et al.
patent: 7714012 (2010-05-01), Honda et al.
patent: 2002/0042535 (2002-04-01), Gribble et al.
patent: 2005/0276836 (2005-12-01), Wilson et al.
patent: 2005/0288363 (2005-12-01), Gribble et al.
patent: 2007/0155742 (2007-07-01), Honda et al.
patent: 2008/0220057 (2008-09-01), Gribble et al.
patent: 2008/0233195 (2008-09-01), Sporn et al.
patent: 2009/0048205 (2009-02-01), Meyer et al.
patent: 2009/0060873 (2009-03-01), Sporn et al.
patent: 2009/0093447 (2009-04-01), Konopleva et al.
patent: 10 2005 04161 (2007-03-01), None
patent: 0 272 891 (1988-06-01), None
patent: 0 329 348 (1995-07-01), None
patent: 0 376 518 (1995-11-01), None
patent: 0 576 230 (1996-04-01), None
patent: 0 577 303 (1997-10-01), None
patent: 0 712 860 (2001-12-01), None
patent: WO 91/15498 (1791-10-01), None
patent: WO 98/00173 (1998-01-01), None
patent: WO 98/32762 (1998-07-01), None
patent: WO 99/33483 (1999-07-01), None
patent: WO 99/65478 (1999-12-01), None
patent: WO 00/73253 (2000-12-01), None
patent: WO 01/01135 (2001-01-01), None
patent: WO 02/03996 (2002-01-01), None
patent: WO 02/47611 (2002-06-01), None
patent: WO 03/043631 (2003-05-01), None
patent: WO 03/059339 (2003-07-01), None
patent: WO 2005/042002 (2005-05-01), None
patent: WO 2005/046732 (2005-05-01), None
patent: WO 2006/029221 (2006-03-01), None
patent: WO 2007/005879 (2007-01-01), None
patent: WO 2007/069895 (2007-06-01), None
patent: WO 2008/111497 (2008-09-01), None
patent: WO 2008/136838 (2008-11-01), None
patent: WO 2009/023232 (2009-02-01), None
Choi et al., Clin Cancer Res 2009; 15; 5258-5266.
Phipps et al., caplus an 2009:547977.
“CDDO in treating patients with metastatic or unresectable solid tumors or lymphoma,” http://www.clinicaltrials.gov/ct2/show/NCT00352040?term=CDDO&rank=1, Dec. 14, 2008.
“FDA mulls drug to slow late-stage Alzheimer's,” http://www.cnn.com/2003/HEALTH/conditions/09/24/alzheimers.drug.ap/index.html, Retrieved on Sep. 23, 2003.
“Phase IIa trail to determine the effects of bardoxolone methyl on renal function in patients with diabetic nephropathy,” http://www.clinicaltrials.gov/ct2/show/NCT00664027?term=rta&rank=10, Dec. 14, 2008.
“RTA 402 in advanced solid tumors or lymphoid malignancies,” http://www.clinicaltrials.gov/ct2/show/NCT00508807?term=rta&rank=2&show—desc=Y, Dec. 14, 2008.
“Study to assess the safety, tolerability, and pharmacodynamics of RTA 402 in patients with the hepatic dysfunction,” http://www.clinicaltrials.gov/ct2/show/NCT00550849?term=rta&rank=4, Dec. 14, 2008.
Abraham and Kappas, “Heme oxygenase and the cardiovascular-renal system,”Free Radic Biol Med., 39(1):1-25, 2005.
Agarwal and Mehta, “Possible involvement of Bc1-2 pathway in resinoid X receptor alpha-induced apoptosis of HL-60 cells,”Biochem Biophys Res Common, 230(2):251-253, 1997.
Ahmad et al., “Triterpenoid CDDO-Me blocks the NF-κB pathway by direct inhibition of IKKβ on Cys-179”,J. Biol. Chem., 281: 35764-9, 2006.
Akrivakis et al., “Prolonged infusion of gemcitabine in stage IV breast cancer: a phase I study,”Anti-Cancer Drugs, 10 (6): 525-531, 1999.
Al-alami et al., “Divergent effect of taxol on proliferation, apoptosis and nitric oxide production in MHH225 CD34 positive and U937 CD34 negative human leukemia cells,”Leukemia Res., 22:939-945, 1998.
Alexander et al., “Synthesis and cytotoxic activity of two novel 1-dodecylthio-2-decyloxypropyl-3-phosphatidic acid conjugates with gemcitabine and cytosine arabinoside,”J. Med. Chem., 46 (19): 4205-4208, 2003.
Ambs et al., “p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells,”Nat. Med., 4(12):1371-1376, 1998.
Amstutz et al., “Die position 5 im oxotremorin-gerust: eine zentrale stelle fur die steuerung der aktivitat am muscarinischen rezeptor,”Helv. Chim. Acta., 70:2232-2244, 1987.
Andreeff et al., “Expression of bcl-2-related genes in normal and AML progenitors: Changes induced by chemotherapy and cationic acid,”Leukemia, 13:1881-1892, 1999.
Andreeff et al., “PPARgamma nuclear receptor as a novel molecular target in leukemias,”2002 Keystone Symposia, Abstract No. 501, 2002.
Andreeff, “Acute myeloid leukemia,”In: Cancer Treatment, Haskell (Ed.), W. B. Saunders, 911-922, 1995.
Araujo et al., “Systemic rather than local heme oxygenase-1 overexpression improves cardiac allograft outcomes in a new transgenic mouse,”J Immunol., 171(3):1572-1580, 2003.
Ardestani et al., “Effects of dexamethasone and betamethasone as COX-2 gene expression inhibitors on rigidity in a rat model of Parkinson's disease,”Indian J. Pharmacol., 39:235-9, 2007.
Ariga et al., “Role of sphingolipid-mediated cell death in neurodegenerative diseases,”Journal of Lipid Research, 39:1-16, 1998.
Bach, “Heme oxygenase-1 and transplantation tolerance,”Hum Immunol. 67(6):430-432, 2006.
Baeuerle, “NF-κB: ten years after,”Cell, 87:13-20, 1996.
Bagasra et al., “Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis,”Proc. Natl. Acad. Sci. USA, 92:12041-12045, 1995.
Baker et al., “2′-Deoxy-2′-methylenecytidine and 2′-deoxy-2′,2′-difluorocytidine 5′-diphosphates: potent mechanism-based inhibitors of ribonucleotide reductase,”J. Med. Chem., 34 (6): 1884, 1991.
Baldwin, “The NF-κB and IκB proteins: new discoveries and insights,”Annu. Rev. Immunol., 14:649-681, 1996.
Balkwill et al., “Smoldering and polarized inflammation in the initiation and promotion of malignant disease,”Cancer Cell, 7 (3): 211-217, 2005.
Bargou et al., “Constitutive nuclear factor κB-Re1A activation is required for proliferation and survival of Hodgkin's disease tumor cells,”J. Clin. Invest., 100:2961-2969, 1997.
Barkett and Gilmore, “Control of apoptosis by Re1/NF-κB transcription factors,”Oncogene, 18:6910-6924, 1999.
Barnes and Karin, “Nuclear factor-κB—a pivotal transcription factor in chronic inflammation diseases,”N. Engl. J. Med., 336:1066-1071, 1997.
Beal, “Mit

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