PRODRUGS OF RILUZOLE AND THEIR METHOD OF USE
Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.
1 - 31 . (canceled)
32 . A method for treating or preventing cancer, said method comprising administering to a subject an effective amount of at least one compound having formula (I):
including enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, and complexes thereof, wherein:
R 1 is CR 10a R 10b NR 11 R 12 ,
R 10a and R 10b are hydrogen,
R 11 is hydrogen,
R 12 is COCR 13a R 13b NR 15a R 15b ,
R 13a and R 13b are hydrogen,
R 15a is hydrogen, and
R 15b is C 1 -C 6 alkyl.
33 . The method of claim 32 , wherein the at least one compound is selected from the group consisting of:
N-methyl-2-(methylamino)-N-(2-oxo-2-((6-(trifluoromethoxy)benzo[d]thiazol-2-yl)amino) ethyl)acetamide;
2-(ethylamino)-N-methyl-N-(2-oxo-2-((6-(trifluoromethoxy)benzo[d]thiazol-2-yl)amino) ethyl)acetamide;
2-(isopropylamino)-N-methyl-N-(2-oxo-2-((6-(trifluoromethoxy)benzo[d]thiazol-2-yl)amino) ethyl)acetamide;
2-(tert-butylamino)-N-methyl-N-(2-oxo-2-((6-(trifluoromethoxy)benzo[d]thiazol-2-yl)amino) ethyl)acetamide;
or a pharmaceutically acceptable form thereof.
34 . The method of claim 32 , wherein the at least one compound is administered in a composition further comprising at least one excipient.
35 . The method of claim 34 , wherein the at least one compound is administered in a composition further comprising an anticancer agent.
36 . The method of claim 35 , wherein the anticancer agent is selected from the group consisting of Vemurafenib, Ipilimumab, Masitinib, Sorafenib, Lenalidomide, Oblimersen, Trametinib, Dabrafenib, RO5185426, Veliparib, Bosentan, YM155, CNTO 95, CR011-vcMMAE, CY503, Lenvatinib, Avastin, Tasidotin, Ramucirumab, IPI-504, Tasisulam, KW2871, MPC-6827, RAF265, Dovitinib, Everolimus, MEK162, BKM120, Nilotinib, Reolysin, 825A, Tremelimumab, PI-88, Elesclomol, STA9090, and Allovectin-7.
37 . The method of claim 32 , wherein the cancer is selected from the group consisting of melanoma, nonmelanoma skin cancer, skin cancer, ovarian cancer, cervical cancer, breast cancer, prostate cancer, testicular cancer, lung cancer, renal cancer, colorectal cancer, brain cancer including glioma and glioblastoma, and leukemia.