Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-02-08
2004-04-27
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S449000, C514S365000
Reexamination Certificate
active
06727276
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the use of certain potent epothilone analogs in the treatment of tumors that have demonstrated resistance to therapy with other chemotherapeutic agents.
BACKGROUND OF THE INVENTION
Epothilones are macrolide compounds that find utility in the pharmaceutical field. For example, epothilones A and B having the structures:
Epothilone A
Epothilone B
R = H
R = Me
may be found to exert microtubule-stabilizing effects similar to paclitaxel (TAXOL®) and hence cytotoxic activity against rapidly proliferating cells, such as tumor cells or other hyperproliferative cellular disease, see Hofle et al.,
Angew. Chem. Int. Ed. Engl
., Vol. 35, No.13/14, 1567-1569 (1996); WO93/10121 published May 27, 1993; and WO97/19086 published May 29, 1997.
Derivatives and analogs of epothilones A and B have been synthesized and may be used to treat a variety of cancers and other abnormal proliferative diseases. Such analogs are disclosed in Hofle et al.,
Id.; Nicolaou
et al.,
Angew. Chem. Int. Ed. Engl
., Vol. 36, No. 19, 2097-2103 (1997); and Su et al.,
Angew. Chem. Int. Ed. Engl
., Vol. 36, No. 19, 2093-2097 (1997). In some instances, epothilone derivatives have demonstrated enhanced properties over the original epothilones A and B. The present invention is concerned with the discovery that two such epothilone derivatives may be utilized to treat certain cancers that have demonstrated resistance to other chemotherapeutic agents, such as oncolytic agents of the taxane family of compounds.
SUMMARY OF THE INVENTION
In accordance with the present invention, tumors demonstrating a clinical resistance to treatment with taxane oncology agents may be treated with an epothilone derivative selected from those represented by formula I:
wherein G, P, Q and R have the meanings given below. The compounds represented by formula I have previously demonstrated significantly enhanced potency over other known chemotherapeutic agents, for example, epothilones A and B above and certain others including those in the taxane series. The compounds represented by formula I are further advantageous in that, unlike most oncology agents, they are efficacious via oral administration.
REFERENCES:
patent: 5969145 (1999-10-01), Schinzer et al.
patent: 6194181 (2001-02-01), Hofmann et al.
patent: 6204388 (2001-03-01), Danishefsky et al.
patent: 6211412 (2001-04-01), Georg et al.
patent: 6242469 (2001-06-01), Danishefsky et al.
patent: 4138042.8 (1993-05-01), None
patent: 19542986.9 (1997-05-01), None
patent: 19639456.2 (1997-05-01), None
patent: 19636343.8 (1998-03-01), None
patent: 19645361.5 (1998-04-01), None
patent: 19645362.3 (1998-04-01), None
patent: 19647580.5 (1998-05-01), None
patent: 19701758 (1998-07-01), None
patent: 19707505.3 (1998-09-01), None
patent: 19713970 (1998-10-01), None
patent: 19720312 (1998-11-01), None
patent: 19821954 (1998-11-01), None
patent: 19726627 (1998-12-01), None
patent: 879 605 (1998-11-01), None
patent: 93/10121 (1993-05-01), None
patent: 97/19086 (1997-05-01), None
patent: 98/08849 (1998-03-01), None
patent: 98/22461 (1998-05-01), None
patent: 98/24427 (1998-06-01), None
patent: 98/25929 (1998-06-01), None
patent: 98/38192 (1998-09-01), None
patent: 98/47891 (1998-10-01), None
patent: 99/01124 (1999-01-01), None
patent: 99/02514 (1999-01-01), None
patent: 99/03848 (1999-01-01), None
patent: 99/07692 (1999-02-01), None
patent: 99/27890 (1999-06-01), None
patent: 99/39694 (1999-08-01), None
patent: 99/42602 (1999-08-01), None
patent: 99/43320 (1999-09-01), None
patent: 99/43653 (1999-09-01), None
patent: 99/54319 (1999-10-01), None
patent: 99/67252 (1999-12-01), None
patent: WQ009967252 (1999-12-01), None
patent: 00/00485 (2000-01-01), None
patent: 00/31247 (2000-06-01), None
patent: 00/37473 (2000-06-01), None
patent: 00/49021 (2000-08-01), None
patent: WO00/050423 (2000-08-01), None
patent: 00/66589 (2000-11-01), None
Balog, A., et al., “Total Synthesis of (−)-Epothilone A”,Angew. Chem. Int. Ed. Engl., vol. 35, No. 23/24, 2801-2803 (1996).
Bertini, F., et al., “Alkenes from Epoxides by Reductive Elimination with Magnesium Bromide-Magnesium Amalgam”,Chem. Commun., 144 (1970).
Bollag, D.M., et al., “Epothilones, A New Class of Microtubule-stabilizing Agents with a Taxol-like Mechanism of Action”,Cancer Res. 55, No. 11, 2325-2333 (1995).
Fujisawa, T., et al., “Deoxygenation of Epoxides to Olefins with FeCl3—n-BuLi System”,Chem. Lett., 883-886 (1974).
Fujiwara, Y., et al., “Reductive Coupling of Carbonyl Compounds to Olefins by Tungsten Hexachloride-Lithium Aluminum Hydride and Some Tungsten and Molybdenum Carbonyls”,J. Org. Chem., vol. 43, No. 12, 2477-2479 (1978).
Gladysz, J. A., et al., “Deoxygenation of Epoxides by Metal Atom Cocondensation”,J. Org. Chem., vol. 41, No. 22, 3647-3648 (1976).
Hofle, G., et al., “Epothilone A and B—Novel 16-Membered Macrolides with Cytotoxic Activity: Isolation, Crystal Structure, and Conformation in Solution”,Angew. Chem. Int. Ed. Engl., vol. 35, No. 13/14, 1567-1569 (1996).
Hofle, G., et al., “N-Oxidation of Epothilone A-C and O-Acyl Rearrangement to C-19 and C-21 -Substituted Epothilones”,Angew. Chem. Int. Ed., vol. 38, No. 13/14, 1971-1974 (1999).
Inokuchi, T., et al., “Opening of Epoxides to Olefins or Halohydrins with Vanadium(II)-Tetrahydrofuran or Vanadium(III)-Tetrahydrofuran Complexes”,Synlett, No. 6, 510-512 (1992).
Kowalski. R. J., et al., “Activities of the Microtubule-stabilizing Agents Epothilones A and B with Purified Tubulin and in Cells Resistant to Paclitaxel (Taxol®)”J. Biol. Chem., vol. 272, No. 4, 2534-2541 (1997).
Kupchan, S. M., et al., “Reductive Elimination of Epoxides to Olefins with Zinc-Copper Couple”,J. Org. Chem., vol. 36, No. 9, 1187-1190 (1971).
Martin, M. G., et al., “Epoxides as Alkene Protecting Groups. A Mild and Efficient Deoxygenation”,Tetrahedron Letters, vol. 25, No. 3, 251-254 (1984).
McMurry, J. E., et al., “Reduction of Epoxides to Olefins with Low Valent Titanium”,J. Org. Chem., vol. 40, No. 17, 2555-2556 (1975).
McMurry, J. E., et al., “Some Deoxygenation Reactions with Low-Valent Titanium (TiCl3/LiAlH4)”,J. Org. Chem., vol. 43, No. 17, 3249-3254 (1978).
Meng, D., et al., “Remote Effects in Macrolide Formation Through Ring-Forming Olefin Metathesis: An Application to the Synthesis of Fully Active Epothilone Congeners”,J. Am. Chem. Soc., vol. 119, No. 11, 2733-2734 (1997).
Nicolaou, K. C., et al., “An Approach to Epothilones Based on Olefin Metathesis”,Angew. Chem. Int. Ed. Engl., vol. 35, No. 20 2399-2401 (1996).
Nicolaou, K. C., et al., “Total Synthesis of Epothilone A: The Macrolactonization Approach”,Angew. Chem. Int. Ed. Engl., vol. 36, No. 5, 525-527 (1997).
Nicolaou, K. C., et. al., “Designed Epothilones: Combinatorial Synthesis, Tubulin Assembly Properties, and Cytotoxic Action against Taxol-Resistant Tumor Cells”,Angew. Chem. Int. Ed. Engl., vol. 36, No. 19, 2097-2103 (1997).
Nicolaou, K.C., et al., “The Olefin Metathesis Approach to Epothilone A and Its Analogues”,J. Am. Chem. Soc., vol. 119, No. 34, 7960-7973 (1997).
Nicolaou, K. C., et al., “Total Syntheses of Epothilones A and B via a Macrolactonization-Based Strategy”,J. Am. Chem. Soc., vol. 119, No. 34, 7974-7991 (1997).
Nicolaou, K. C., et al., “Synthesis of Epothilones A and B in Solid and Solution Phase”,Nature, vol. 387, 268-272 (1997).
Nicolaou, K. C., et al., “Synthesis of Epothilones A and B in Solid and Solution Phase” (Correction toNature387, 268-272 (1997)),Nature, 390, 100 (1997).
Raucher, S., et al., “Total Synthesis of (+)-Dihydrocostunolide via Tandem Cope-Claisen Rearrangement”,J. Org. Chem., vol. 51, No. 26, 5503-5505 (1986).
Sato, M, et al., “Reduction of Organic Compounds with Low-Valent Niobium (NbCl5/NaAlH4)”,Chem. Letters, 157-160 (1982).
Schinzer, D., et al., “Total Synthesis of (−)-Epothilone A”,Angew. Chem. Int. Ed. Engl., vol. 36, No. 5, 523-524 (1997).
Schobert, R., et al., “Reduction and Isomerization of Oxiranes and &agr;-Diazoketones by Various Early Transition Metallocenes”,Synlett, vol. 8, 465-466 (1990).
Sharpless, K. B., et al., “L
Bristol--Myers Squibb Company
Criares Theodore J.
Patel Rena
Winslow Anastasia P.
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