Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-08-09
2004-02-10
Kifle, Bruck (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C540S456000, C540S462000
Reexamination Certificate
active
06689802
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to crystalline polymorphic forms of a highly potent epothilone analog that is characterized by enhanced properties.
BACKGROUND OF THE INVENTION
Epothilones are macrolide compounds that find utility in the pharmaceutical field. For example, Epothilones A and B having the structures:
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, G., et al.,
Angew. Chem. Int. Ed. Engl.,
Vol. 35, No.13/14, 1567-1569 (1996); W093/10121 published May 27, 1993; and WO97/19086 published May 29, 1997.
Various epothilone analogs 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, K. C., et al.,
Angew Chem. Int. Ed. Engl.
Vol. 36, No. 19, 2097-2103 (1997); and Su, D.-S., et al.,
Angew Chem. Int. Ed. Engl.,
Vol. 36, No. 19, 2093-2097 (1997).
A particularly advantageous epothilone analog that has been found to have advantageous activity is [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione. In accordance with the present invention, two crystal forms of the subject epothilone analog are provided. These polymorphs, which have been designated as Forms A and B, respectively, are novel crystal forms and are identified hereinbelow.
REFERENCES:
patent: 6194181 (2001-02-01), Hofmann et al.
patent: 6204388 (2001-03-01), 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: 99/03848 (1999-01-01), None
patent: 99/07692 (1999-02-01), 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: 99/27890 (1999-10-01), None
patent: 00/00485 (2000-01-01), None
patent: 00/37473 (2000-06-01), 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”,Agnew. 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 Soild 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 •-Diazoketones by Various Early Transition Metallocenes”,Synlett,Vol. 8, 465-466 (1990).
Sharpless, K. B., et al., “Lower Valent Tungsten Halides. A New Class of Reagents for Deoxygenation of Organic Molecules”,J. Amer. Chem. Soc.,Vol. 94, No.18, 6538-6540 (1972).
Su, D.-S., et al., “Total Synthesis of (−)-Epothilone B: An Extension of the Suzuki Coupling Method and Insights into Structure-Activity Relationships of the Epothilones”,Angew. Chem. Int. Ed. Engl.,Vol. 36, No. 7, 757-759 (1997).
Su, D.-S., et al., “Structure-Activity Relationships of the Epothilones and the First in vivo Comparison with Paclitaxel”,Angew. Chem. Int. Ed. Engl.,Vol. 36, No. 19, 2093-2096 (1997).
Victory, S. F., et al., “Relative Stereochemistry and Solution Conformation of the Novel Paclitaxel-Like Antimitotic Agent Epothilone A”,Bioorg. Med. Chem. Letts.,Vol. 6, No. 7, 893-898 (1996).
Winkler, J. D., et al., “A Model for the Taxol (Paclitaxel)/Epothilone Pharmacophore”,Bioorg. Med. Chem. Letts.,Vol. 6, No. 24, 2963-2966 (1996).
Yang, Z., et al., “Total Synthesis of Epothilone A: The Olefin Metathesis Approach”,Angew. Chem. Int. Ed. Engl
Davidovich Martha
DiMarco John D.
Favreau Denis
Galella Michael A.
Gougoutas Jack Z.
Bristol--Myers Squibb Company
Kifle Bruck
Patel Rena
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