Claims for Patent: 7,087,621

Summary for Patent: 7,087,621

Title:	Benzo- and azabenzodithiazole compounds
Abstract:	The present invention provides compounds of formula I ##STR00001## or a pharmaceutically acceptable salt, solvate, prodrug or isomer thereof and compounds of the formula ##STR00002## or a pharmaceutically acceptable salt, solvate, prodrug or isomer thereof. The compounds of the invention inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents. The compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.
Inventor(s):	Sang; Xiaopeng (Glastonbury, CT), Du; Xuhua Karen (Cheshire, CT), Kadow; John F. (Wallingford, CT)
Assignee:	Bristol-Myers Squibb Company (Princeton, NJ)
Application Number:	10/933,094
Patent Claims:	1. A compound of formula I ##STR00021## wherein the symbols have the following meanings and are, for each occurrence, independently selected: R.sup.1 is one or more hydrogen, alkyl, aryl, halogen, CF.sub.3, NH.sub.2, NO.sub.2, cyano, COOH, COOalkyl, CONR.sub.3R.sub.4, NHCOalkyl, NHCOaryl, NHSO.sub.2alkyl, NHSO.sub.2aryl or NHCOalkoxyaryl, said aryl groups optionally substituted with one or more groups selected from alkyl, NO.sub.2 or halogen; R.sup.2 is one or more alkoxy, hydroxy, aryloxy, NHCOalkyl, CONR.sub.3R.sub.4, CF.sub.3 or NO.sub.2; R.sup.3 and R.sup.4 are independently hydrogen, alkyl, substituted alkyl, halogen, alkoxy, substituted alkoxy, aryl or substituted aryl; or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof. 2. A compound of formula II ##STR00022## wherein the symbols have the following meanings and are, for each occurrence, independently selected: R.sup.1 is one or more hydrogen, alkyl, aryl, halogen, CF.sub.3, NR.sub.3R.sub.4, NO.sub.2, cyano, COOH, COOalkyl, CONR.sub.3R.sub.4, NHCOalkyl, NHCOaryl, NHSO.sub.2alkyl or NHSO.sub.2aryl, said aryl groups optionally substituted with one or more groups selected from alkyl, NO.sub.2 or halogen; R.sup.2is one or more alkyl, alkoxy, halogen, aryloxy, NHCOalkyl, CONR.sub.3R.sub.4, CF.sub.3 or NO.sub.2; R.sup.3 and R.sup.4 are independently hydrogen, alkyl, substituted alkyl, halogen, alkoxy, substituted alkoxy, aryl or substituted aryl; and one or more of W, X, Y and Z is N; or a pharmaceutically acceptable salt, solvate, prodrug or steroisomer thereof. 3. The compound according to claim 1 wherein R.sup.1 is one or more hydrogen, halogen, CF.sub.3, NH.sub.2, NO.sub.2, COOH, COOalkyl, CONR.sub.3R.sub.4, NHCOalkyl, NHCOaryl, NHSO.sub.2alkyl, NHSO.sub.2aryl or NHCOalkoxyaryl, said aryl groups optionally substituted with one or more groups selected from alkyl, NO.sub.2 or halogen; R.sup.2 is one or more alkoxy, hydroxy, aryloxy, NHCOalkyl, CONR.sub.3R.sub.4, CF.sub.3 or NO.sub.2; R.sup.3 and R.sup.4 are independently hydrogen or, alkyl; or a pharmaceutically acceptable salt, solvate, prodrug or steroisomer thereof. 4. The compound according to claim 2 wherein R.sup.1 is one or more hydrogen, NR.sub.3R.sub.4, NO.sub.2, CONR.sub.3R.sub.4, NHCOalkyl or NHCOaryl; R.sup.2 is one or more alkyl, alkoxy, halogen or aryloxy, CF.sub.3 or NO.sub.2; R.sup.3 and R.sup.4 are independently hydrogen or, alkyl; X is N and W,Y and Z are --CH--; or a pharmaceutically acceptable salt, solvate, prodrug or steroisomer thereof. 5. A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically acceptable carrier. 6. A pharmaceutical composition comprising at least one compound of claim 1 in combination with a pharmaceutically acceptable carrier and at least one other anti-cancer or cytotoxic agent which is selected from the group consisting of tamoxifen, toremifen, raloxifene, droloxifene, iodoxifene, megestrol acetate, anastrozole, letrozole, borazole, exemestane, flutamide, nilutamide, bicalutamide, cyproterone acetate, gosereline acetate, leuprolide, finasteride, marimastat, bevacizumab, cetuximab, methotrexate, 5-fluorouracil, purine, cytosine arabinoside, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin, mithramycin, cisplatin, carboplatin, nitrogen mustard, melphalan, chlorambucil, busulphan, cyclophosphamide, ifosfamide, nitrosoureas, thiotepa, vincristine, paditaxel, docetaxel, etoposide, teniposide, amsacrine, topotecan, flavopyridols, and bortezomib, kinase inhibitors, methotrexate, 5-fluorouracil, purine, adenosine analogues, cytosine arabinoside, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin, mithramycin, cisplatin, carboplatin, nitrogen mustard, melphalan, chlorambucil, busulphan, cyclophosphamide, ifosfamide, nitrosoureas, thiotepa, vincristine, paclitaxel, docetaxel, epothilone analogs, discodermolide analogs, eleutherobin analogs, etoposide, teniposide, amsacrine, topotecan, flavopyridols, proteasome inhibitors including bortezomib and biological response modifiers. 7. A pharmaceutical composition comprising at least one compound of claim 2 and a pharmaceutically acceptable carrier. 8. A pharmaceutical composition comprising at least one compound of claim 2 in combination with a pharmaceutically acceptable carrier and at least one other anti-cancer or cytotoxic agent which is selected from the group consisting of tamoxifen, toremifen, raloxifene, droloxifene, iodoxifene, megestrol acetate, anastrozole, letrozole, borazole, exemestane, flutamide, nilutamide, bicalutamide, cyproterone acetate, gosereline acetate, leuprolide, finasteride, marimastat, bevacizumab, cetuximab, methotrexate, 5-fluorouracil, purine, cytosine arabinoside, doxorubicin, daunomycin, epirubicin, idarubicin, mitomvcin-C, dactinomycin, mithramycin, cisplatin, carboplatin, nitrogen mustard, melphalan, chlorambucil, busulphan, cyclophosphamide, ifosfamide, nitrosoureas, thiotepa, vincristine, paditaxel, docetaxel, etoposide, teniposide, amsacrine, topotecan, flavopyridols, and bortezomib.

Details for Patent 7,087,621

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2023-09-05
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2023-09-05
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2023-09-05