STABLE SNS-595 COMPOSITIONS AND METHODS OF PREPARATION
Methods of preparing substantially pure SNS-595 substance are disclosed. Also provided are compositions comprising SNS-595 substance that are substantially pure and essentially free of visible particles.
1 - 32 . (canceled)
33 . A method of treating cancer comprising administering to a subject having cancer a therapeutically effective amount of a composition, the composition comprising substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance, wherein the substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance comprises 0 to 0.02% Compound 4
and 0 to 0.02% Compound 5
based on total weight of the substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance.
34 . The method of claim 33 , wherein the composition consists essentially of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, 0 to 0.02% Compound 4, and 0 to 0.02% Compound 5 based on total weight of the composition.
35 . The method of claim 33 , wherein the composition is in an aqueous solution in water, and where about 100 mg of substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance is present for every 10 mL of the aqueous solution, and the aqueous solution maintains not more than 1000 particles≥10 microns per 10 mL of the aqueous solution when stored for at least 1 month.
36 . A method of treating cancer comprising administering to a subject having cancer a therapeutically effective amount of a composition, the composition comprising substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance, wherein the substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance comprises 0 to 0.02% Compound 4
and 0 to 0.1% Compound 7
based on total weight of the substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance.
37 . The method of claim 36 , wherein the substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid further comprises 0 to 0.02% Compound 5
based on total weight of the substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid substance.
38 . The method of claim 36 , wherein the composition consists essentially of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, 0 to 0.02% Compound 4, 0 to 0.1% Compound 7 and 0 to 0.02% Compound 5 based on total weight of the composition.
39 . The method of claim 36 , wherein the composition is in an aqueous solution in water, and where about 100 mg of substantially pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy substance is present for every 10 mL of the aqueous solution, and the aqueous solution maintains not more than 1000 particles≥10 microns per 10 mL of the aqueous solution when stored for at least 1 month.
40 . The method of claim 33 , wherein the cancer is acute myeloid leukemia.
41 . The method of claim 36 , wherein the cancer is acute myeloid leukemia.