Sulfonyl amide derivatives for the treatment of abnormal cell growth

Abstract

The present invention relates to a compound of the formula I wherein R 1 to R 6 , A, B, n and m are as defined herein. Such novel sulfonyl amide derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

1 - 20 . (canceled) 
     
     
         21 . A method of making a compound of Formula (B2), the method comprising: 
       
         
           
           
               
               
           
         
         reacting a compound of Formula (B 1) 
       
       
         
           
           
               
               
           
         
         with hydrogen, thereby providing the compound of Formula (B2). 
       
     
     
         22 . The method of  claim 21 , wherein the reaction is performed in the presence of a catalyst. 
     
     
         23 . The method of  claim 22 , wherein the catalyst is 10% palladium on carbon. 
     
     
         24 . The method of  claim 21 , wherein the reaction is performed in the presence of a solvent. 
     
     
         25 . The method of  claim 24 , wherein the solvent is 2N methanolic NH 2 . 
     
     
         26 . The method of  claim 21 , wherein the reaction of the compound of Formula (B1) with hydrogen is performed under hydrogen pressure. 
     
     
         27 . The method of  claim 26 , wherein the pressure is 45 psi. 
     
     
         28 . The method of  claim 21 , wherein the reaction is performed in a Parr reactor. 
     
     
         29 . The method of  claim 21 , wherein the reaction is performed at ambient temperature. 
     
     
         30 . The method of  claim 29 , wherein the temperature is 25° C. 
     
     
         31 . The method of  claim 21 , wherein the reaction is performed for 3 hours. 
     
     
         32 . The method of  claim 21 , further comprising isolating the compound of Formula (B2), wherein isolating the compound of Formula (B2) comprises filtration. 
     
     
         33 . The method of  claim 32 , wherein the filtration is through Celite. 
     
     
         34 . The method of  claim 21 , wherein the compound of Formula (B1) is made by a method which comprises reacting a compound of Formula (B0) 
       
         
           
           
               
               
           
         
         with N-methyl-methane sulfonamide, 
       
       
         
           
           
               
               
           
         
         thereby providing the compound of Formula (B1). 
       
     
     
         35 . The method of  claim 34 , wherein the reaction is performed in the presence of a solvent. 
     
     
         36 . The method of  claim 35 , wherein the solvent is acetonitrile. 
     
     
         37 . The method of  claim 34 , wherein the reaction is performed in the presence of a base. 
     
     
         38 . The method of  claim 37 , wherein the base is cesium carbonate. 
     
     
         39 . The method of  claim 36 , wherein the reaction is added at ambient temperature. 
     
     
         40 . The method of  claim 39 , wherein the temperature is 25° C. 
     
     
         41 . The method of  claim 34 , wherein the reaction is performed at elevated temperature. 
     
     
         42 . The method of  claim 41 , wherein the temperature is 80° C. 
     
     
         43 . The method of  claim 34 , further comprising isolating the compound of Formula (B1), wherein isolating the compound of Formula (B1) comprises decreasing the temperature of the reaction mixture to ambient temperature. 
     
     
         44 . The method of  claim 43 , wherein the temperature is 25° C. 
     
     
         45 . The method of  claim 43 , wherein isolating the compound of Formula (B1) comprises filtration. 
     
     
         46 . The method of  claim 34 , wherein the compound of Formula (B1) is purified using column chromatography.