Tricyclic-bis-enone derivatives and methods of use thereof

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C558S429000

Reexamination Certificate

active

10345053

ABSTRACT:
Novel tricyclic-bis-enone derivatives (TBEs) as well as the process for the preparation of such TBEs are provided. Also provided are methods for prevention and/or treatment of cancer, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotropic lateral sclerosis, rheumatoid arthritis, inflammatory bowel disease, and all other diseases whose pathogenesis is believed to involve excessive production of either nitric oxide (NO) or prostaglandins or the overexpression of iNOS or COX-2 genes or gene products. Further, methods for the synthesis of the TBE compounds of the invention utilize cheap commercially available reagents and are highly cost effective and amenable to scale-up. Additional high efficiency synthetic methods that utilize novel intermediates as well as the synthesis of these intermediates are also provided. Furthermore, the invention also provides methods for designing novel and water-soluble TBEs.

REFERENCES:
patent: 6326507 (2001-12-01), Gribble et al.
patent: WO 99/65478 (1999-12-01), None
patent: WO 00/73253 (2000-12-01), None
Baeuerle, “NF-κB: ten years afters,”Cell,87:13-20, 1996.
Baldwin, “The NF-κB and IκB proteins: new discoveries and insights,”Annu. Rev. Immunol.,14:649-681, 1996.
Bargou et al., “Constitutive nuclear factor κB-RelA 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 Rel/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.
Bogdan et al., “Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-β and interleukin-10,”J. Biol. Chem.,267:23301-23308, 1992.
Clinton et al., “Steroidal[3,2-c]pyrazoles. II. Androstanes, 19-norandrostanes and their unsaturated analogs,”J. Am. Chem. Soc.,83:1478-1491, 1961.
Ding et al., “Macrophage deactivating factor and transforming growth factors-β1β2and β3, inhibit induction of macrophage nitrogen oxide synthesis by IFNγ1,”J. Immunol.,940-944, 1990.
DuBios et al., “Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors,”Gastroenterology,110:1259-1262, 1996.
DuBois et al., “G1delay in cells overexpressing prostaglandin endoperoxide synthase-21,”Cancer Res.,56(4):733-737, 1996.
Dutcher et al., “Pentacyclic triterpene synthesis. 5. Synthesis of optically pure ring AB precursors,”J. Org. Chem.,41:2663-2669, 1976.
Favaloro et al., “Design and synthesis of tricyclic compounds with enone functionalities in rings A and C: a novel class of highly active inhibitors of nitric oxide production in mouse macrophages,”J. Med. Chem.,45:4801-4805, 2002.
Ghosh et al., “NF-κB and Rel proteins: evolutionarily conserved mediators of immune response,”Annu Rev Immunol.,16:225-260, 1998.
Grieco et al., “Synthetic studies on quassinoids: total synthesis and biological evaluation of (+)-des-D-chaparrinone,”J. Org. Chem.,63:5929-5936, 1998.
Hirota et al., “Stereoselective total synthesis of (±)-eperuane-8β,15-diol1,”Bull. Chem. Soc. Jpn.,61:4023-4028, 1988.
Hirota et al., “Total synthesis of (±)-amarolide, a quassinoid bitter principle,”J. Org. Chem.,56:1119-1127, 1991.
Honda et al., “Novel synthetic oleanane triterpenoids: a series of highly active inhibitors of nitric oxide production in mouse macrophages,”Bioorg. Med. Chem. Lett.,9(24):3429-3434, 1999.
Honda et al., “Synthesis of (±)-3,3-ethylenedioxy-14α-hydroxy-5-picrasene-11,16-dione, a 14αH-picrasane derivative,”Chem. Lett.,299-302, 1981.
Honda et al., “Synthetic oleanane and ursane triterpenoids with modified rings A and C: A series of highly active inhibitors of nitric oxide production in mouse macrophages,”J. Med. Chem.,43:4233-4246, 2000.
Honda, et al., “Novel synthetic oleanane and ursane triterpenoids with various enone functionalities in ring A as inhibitors of nitric oxide production in mouse macrophages,”J. Med. Chem.,43:1866-1877, 2000.
Huang et al., “Structure of a WW domain containing fragment of dystrophin in complex with β-dystroglycan,”Nat. Struct. Biol.,7:634-638, 2000.
Ito et al., “Involvement of caspase-8 in the induction of osteosarcoma cell apoptosis by the novel triterpenoid CDDO,”47thAnnual Meeting, Orthopaedic Research Society,Feb. 25-28, 2001, San Francisco, California, p. 0863, Poster Session, 2001.
Ito et al., “The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism,”Cell Growth Differ.,11:261-267, 2000.
Ito et al., “The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism,”Mol. Pharmacol.,59:1094-1099, 2001.
Johnson et al., “A plan for distinguishing between some five- and six-membered ring ketones,”J. Am. Chem. Soc.,67:1745-1754, 1945.
Kerwin et al., “Quassinoid synthesis. 2. Preparation of a tetracyclic intermediate having the Bruceantin tetrahydrofuran ring,”J. Org. Chem.,52:1686-1695, 1987.
Mix et al., “A synthetic triterpenoid selectively inhibits the induction of matrix metalloproteinases 1 and 13 by inflammatory cytokines,”Arthritis Rheum.,44:1096-1104, 2001.
Muzart, “Synthesis of unsaturated carbonyl compounds via a chromium-mediated allylic oxidation by 70% tert.butylhydroperoxide,”Tetrahedron Lett.,28:4665-4668, 1987.
Pahl, “Activators and target genes of Rel/NF-κB transcription factors,”Oncogene,18:6853-6866, 1999.
Prescott and White, “Self-promotion? Intimate connections between APC and prostaglandin H synthase-2,”Cell,87(5):783-786, 1996.
Rayet and Gelinas, “Aberrant rel
fkb genes and activity in human cancer,”Oncogene,18:6938-6947, 1999.
Sheng et al., “A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells,”Gastroenterology,113(6):1883-18891, 1997.
Snitman et al., “Synthetic approaches to taxodione synthesis of methyl 12-oxopodocarpa-5,9(11)-diene-8β-carboxylate,”Synth. Comm.,8:187-194, 1978.
Sporn and Roberts, “Peptide growth factors and inflammation, tissue repair, and cancer,”J. Cvlin. Invest.,78:329-332, 1986.
Suh et al., “A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid with potent differentiating, antiproliferative, and anti-inflammatory activity,”Cancer Res.,59(2):336-341, 1999.
Suh et al., “Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages,”Cancer Research,58:717-723, 1998.
Tsujii and DuBois, “Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2,”Cell,83(3):493-501, 1995.
Wang et al., “A synthetic Triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor γ,”Mol. Endocrin.,14(10):1550-1556, 2000.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Tricyclic-bis-enone derivatives and methods of use thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Tricyclic-bis-enone derivatives and methods of use thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Tricyclic-bis-enone derivatives and methods of use thereof will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3865745

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.