Claims for Patent: 7,211,593

Summary for Patent: 7,211,593

Title:	C12-cyano epothilone derivatives
Abstract:	The present invention relates to compounds useful in the treatment of cancer or other proliferative diseases represented by the formula ##STR00001## wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 are hydrogen or lower alkyl; R.sub.6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, or heterocyclo; X is hydrogen and Y is hydroxy, or X and Y taken together represent a carbon-carbon bond; and pharmaceutically acceptable salts, solvates, or hydrates thereof. Also included are therapeutic compositions containing the compounds represented by formula I as active ingredients, alone or in combination with other therapeutic agents useful in the treatment of cancer or other proliferative diseases.
Inventor(s):	Vite; Gregory D. (Titusville, NJ), Regueiro-Ren; Alicia (Middletown, CT)
Assignee:	Bristol-Myers Squibb Co. (Princeton, NJ)
Application Number:	10/386,059
Patent Claims:	1. A compound represented by formula I: ##STR00020## wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are independently selected from hydrogen and lower alkyl; R.sub.6 is optionally-substituted thiazolyl; X is hydrogen and Y is hydroxy, or X and Y taken together represent a carbon-carbon bond; and steroisomers, pharmaceutically acceptable salts, solvates and/or hydrates thereof. 2. The compound of claim 1 wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each methyl. 3. The compound of claim 2 wherein: R.sub.6 is selected from the group consisting of: ##STR00021## 4. The compound of claim 1 wherein X is hydrogen and Y is hydroxy. 5. The compound of claim 1 wherein said compound is selected from the group consisting of: [1S, 5S, 6S, 7R, 10S, 14S(E), 16S]-1-Cyano-6,10-dihydroxy-5,7,9,9-tetramethyl-14-[1-methyl-2-(2-methyl-- 4-thiazolyl)ethenyl]-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione; [1S, 5S, 6S, 7R, 10S, 14S(E), 16S]-1-Cyano-6,10-dihydroxy-5,7,9,9-tetramethyl-14-[1-methyl-2-(2-hydroxy- methyl-4-thiazolyl)ethenyl]-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dio- ne; [1S, 5S, 6S, 7R, 10S, 14S(E), 16S]-1-Cyano-6,10-dihydroxy-5,7,9,9-tetramethyl-14-[1-methyl-2-(2-azidome- thyl-4-thiazolyl)ethenyl]-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione- ; and [1S, 5S, 6S, 7R, 10S, 14S(E), 16S]-1-Cyano-6,10-dihydroxy-5,7,9,9-tetramethyl-14-[1-methyl-2-(2-aminome- thyl-4-thiazolyl)ethenyl]-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione- ; and pharmaceutically acceptable salts, solvates or hydrates thereof. 6. A pharmaceutical composition comprising as an active ingredient at least one compound of claim 1, or a pharmaceutically acceptable salt, solvate, and/or thereof, and one or more pharmaceutically acceptable carriers, excipients and/or diluents. 7. The pharmaceutical composition of claim 6 additionally comprising as a further active ingredient a therapeutic agent useful in the treatment of cancer or other proliferative diseases. 8. The pharmaceutical composition of claim 7 wherein said therapeutic agent useful in the treatment of cancer or other proliferative diseases is selected from the group consisting of adriamycin, cisplatin, carboplatin, cimetidine, carminomycin, mechlorethamine hydrochloride, pentamethylmelamine, thiotepa, teniposide, cyclophosphamide, chlorambucil, demethoxyhypocrellin A, melphalan, ifosfamide, trofosfamide, Treosulfan, podophyllotoxin or podophyllotoxin derivatives, etoposide phosphate, teniposide, etoposide, leurosidine, leurosine, vindesine, 9-aminocamptothecin, camptoirinotecan, crisnatol, Chloroambucil, megestrol, methopterin, mitomycin C, ecteinascidin 743, busulfan, carmustine (BCNU), lomustine (CCNU), lovastatin, 1-methyl-4-phenylpyridinium ion, semustine, staurosporine, streptozocin, thiotepa, phthalocyanine, dacarbazine, aminopterin, methotrexate, trimetrexate, thioguanine, mercaptopurine, fludarabine, pentastatin, cladribin, cytarabine (ara C), porfiromycin, 5-fluorouracil, 6-mercaptopurine, doxorubicin hydrochloride, leucovorin, mycophenoloc acid, daunorubicin, deferoxamine, floxuridine, doxifluridine, ratitrexed, idarubicin, epirubican, pirarubican, zorubicin, mitoxantrone, bleomycin sulfate, mitomycin C, actinomycin D, safracins, saframycins, quinocarcins, discodermolides, vincristine, vinblastine, vinorelbine tartrate, vertoporfin, paclitaxel, tamoxifen, raloxifene, tiazofuran, thioguanine, ribavirin, EICAR, estramustine, estramustine phosphate sodium, flutamide, bicalutamide, buserelin, leuprolide, pteridines, diyneses, levamisole, aflacon, interferon, interleukins, aldesleukin, filgrastim, sargramostim, rituximab, BCG, tretinoin, irinotecan hydrochloride, betamethosone, gemcitabine hydrochloride, verapamil, VP-16, altretamine, thapsigargin and topotecan. 9. A unit dosage form of a pharmaceutical composition comprising a compound of claim 1. 10. A sterile injectable unit dosage form of a pharmaceutical composition comprising a compound of claim 1. 11. The unit dosage form of claim 9 wherein said dosage form is lyophilized. 12. The unit dosage form of claim 10 wherein said dosage form is lyophilized. 13. A compound of claim 3 wherein X is hydrogen and Y is hydroxy. 14. A compound of claim 1 wherein: R.sub.6 is selected from the group consisting of: ##STR00022## 15. A compound of claim 14 wherein X is hydrogen and Y is hydroxy. 16. A pharmaceutical composition comprising as an active ingredient at least one compound of claim 3, or a pharmaceutically-acceptable salt, solvate, and/or hydrate thereof, and one or more pharmaceutically-acceptable carriers, excipients and/or diluents. 17. A pharmaceutical composition comprising as an active ingredient at least one compound of claim 13, or a pharmaceutically-acceptable salt, solvate, and/or hydrate thereof, and one or more pharmaceutically-acceptable carriers, excipients and/or diluents. 18. A pharmaceutical composition comprising as an active ingredient at least one compound of claim 14, or a pharmaceutically-acceptable salt, solvate, and/or hydrate thereof, and one or more pharmaceutically-acceptable carriers, excipients and/or diluents. 19. A pharmaceutical composition comprising as an active ingredient at least one compound of claim 15, or a pharmaceutically-acceptable salt, solvate, and/or hydrate thereof, and one or more pharmaceutically-acceptable carriers, excipients and/or diluents.

Details for Patent 7,211,593

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Clinigen, Inc.	PROLEUKIN	aldesleukin	For Injection	103293	05/05/1992		2022-03-12
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2022-03-12
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2022-03-12
Partner Therapeutics, Inc.	LEUKINE	sargramostim	For Injection	103362	03/05/1991		2022-03-12