Stable sns-595 compositions and methods of preparation

Abstract

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.