Claims for Patent: 9,381,260

Summary for Patent: 9,381,260

Title:	Hypoxia inducible factor-1 pathway inhibitors and uses as anticancer and imaging agents
Abstract:	This disclosure relates to Hypoxia Inducible Factor-1 pathway inhibitors and uses as anticancer and imaging agents. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions disclosed herein.
Inventor(s):	Mun; Jiyoung (Atlanta, GA), Goodman; Mark M. (Atlanta, GA), Van Meir; Erwin G. (Tucker, GA)
Assignee:	Emory University (Atlanta, GA)
Application Number:	13/728,821
Patent Claims:	1. A compound of the formula ##STR00027## or salts thereof, wherein X is selected from hydroxy and methoxy, wherein X is optionally substituted with one or more, the same or different R.sup.1; Y is selected from alkyl, isopropyl, and isobutyl wherein Y is optionally substituted with one or more, the same or different R.sup.1; Z is 2-pyridinyl, 4-pyridinyl wherein Z is optionally substituted with one or more, the same or different R.sup.1; R.sup.1 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl).sub.2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R.sup.1 is optionally substituted with one or more, the same or different, R.sup.2; and R.sup.2 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl. 2. The compound of claim 1 wherein the compound comprises a carbon 11 or fluorine 18 radionuclide. 3. The compound of claim 1 selected from: N-((8-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methyl)-N-isobutylpyridine-4-s- ulfonamide; N-((8-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methyl)-N-isobutylpyridine-2-s- ulfonamide; N-[(8-Methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridin- e-2-sulfonamide; N-[(8-Hydroxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridin- e-2-sulfonamide; and N-[(8-Hydroxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridin- e-4-sulfonamide. 4. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt and a pharmaceutically acceptable excipient. 5. A method of treating cancer comprising administering an effective amount of a pharmaceutical composition of claim 4. 6. The method of claim 5, wherein the cancer is selected from glioblastoma (GBM), breast, pancreatic, colon, metastatic lung cancers, bladder cancer, lung cancer, breast cancer, melanoma, colon and rectal cancer, non-hodgkin lymphoma, endometrial cancer, pancreatic cancer, kidney cancer, prostate cancer, leukemia, thyroid cancer, and brain cancer. 7. The method of claim 6, wherein the composition is administered in combination with a second anti-cancer agent. 8. The method of claim 7, wherein the second anti-cancer agent is temozolamide, bevacizumab, procarbazine, lomustine, vincristine, gefitinib, erlotinib, docetaxel, cis-platin, 5-fluorouracil, gemcitabine, tegafur, raltitrexed, methotrexate, cytosine arabinoside, hydroxyurea, adriamycin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin and mithramycin, vinblastine, vindesine, vinorelbine, taxol, taxotere, etoposide, teniposide, amsacrine, topotecan, camptothecin, bortezomib, anagrelide, tamoxifen, toremifene, raloxifene, droloxifene, iodoxyfene, fulvestrant, bicalutamide, flutamide, nilutamide, cyproterone, goserelin, leuprorelin, buserelin, megestrol, anastrozole, letrozole, vorazole, exemestane, finasteride, marimastat, trastuzumab, cetuximab, dasatinib, imatinib, combretastatin, thalidomide, and/or lenalidomide or combinations thereof. 9. A method of imaging a tumor comprising administering a compound of claim 2 to a subject and viewing the compound by PET.

Details for Patent 9,381,260

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2039-02-26
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2039-02-26
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2039-02-26
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2039-02-26