P-toluenesulfonate for mek kinase inhibitor, method of preparation thereof, and method of use thereof

Abstract

Disclosed are a p-toluenesulfonate of a MEK kinase inhibitor, and a crystal form thereof and a preparation method thereof. Specifically disclosed are a 2-((2-fluorine-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridine-3-group)oxygroup)-6-carbonyl-1,6-dihydropyridine-3-formamide p-toluenesulfonate (a compound represented by formula (I)), a crystal form I, and a preparation method thereof. The obtained crystal form I of the compound of formula (I) has good crystal form stability and chemical stability, and the crystallization solvent used has low toxicity and low residue, and is more suitable for use in clinical treatment.

1 . 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridin-3-yl)oxy)-6-oxo-1,6-dihydropyridine-3-carboxamide p-toluenesulfonate of formula (I), 
       
         
           
           
               
               
           
         
       
     
     
         2 . (canceled) 
     
     
         3 . A method of preparing the 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridin-3-yl)oxy)-6-oxo-1,6-dihydropyridine-3-carboxamide p-toluenesulfonate of formula (I) according to  claim 1 , comprising reacting p-toluenesulfonic acid with 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridin-3-yl)oxy)-6-oxo-1,6-dihydropyridine-3-carboxamide. 
     
     
         4 .- 5 . (canceled) 
     
     
         6 . A pharmaceutical composition comprising the 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridin-3-yl)oxy)-6-oxo-1,6-dihydropyridine-3-carboxamide p-toluenesulfonate of formula (I) according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         7 . (canceled) 
     
     
         8 . A method of inhibiting MEK kinase in a subject, the method comprising administering to the subject the pharmaceutical composition according to  claim 6 . 
     
     
         9 . A method of treating melanoma in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to  claim 6 . 
     
     
         10 . A method of inhibiting MEK kinase in a subject, the method comprising administering to the subject the 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridin-3-yl)oxy)-6-oxo-1,6-dihydropyridine-3-carboxamide p-toluenesulfonate of formula (I) according to  claim 1 . 
     
     
         11 . A method of treating melanoma in a subject in need thereof, the method comprising administering to the subject the 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridin-3-yl)oxy)-6-oxo-1,6-dihydropyridine-3-carboxamide p-toluenesulfonate of formula (I) according to  claim 1 .