Thiolactams and uses thereof

Abstract

This invention provides compounds of formula I: wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as described in the specification. The compounds are inhibitors of PLK and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

1 - 35 . (canceled) 
     
     
         36 . A process for preparing a compound of formula III: 
       
         
           
           
               
               
           
         
       
       wherein R 4  and R 6  are each H, R 3  is methyl, R 5  is X—R 5a , wherein X is an optionally substituted C 3  alkylene chain, and R 5a  is —N(Me) 2 ,
 the process comprising the steps of:
 (e-1) treating a compound of formula V: 
 
 
       
         
           
           
               
               
           
         
         
            with a compound of formula VI: 
         
       
       
         
           
           
               
               
           
         
         
            in the presence of Pd(PPh 3 ) 2 Cl 2 , CuI, and triethylamine to give a compound of formula VII: 
         
       
       
         
           
           
               
               
           
         
         
           (e-2) hydrogenating the compound of formula VII with hydrogen and Pd(OH) 2  in the presence of a suitable solvent, such as isopropyl alcohol, followed by treatment with HCl to give a compound of formula VIII: 
         
       
       
         
           
           
               
               
           
         
         
           (e-3) treating the compound of formula VIII with a compound of formula IX: 
         
       
       
         
           
           
               
               
           
         
         
            in the presence of acetic acid and acetonitrile to give the compound of formula III. 
         
       
     
     
         37 . A compound of formula Ill: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein
 R 3  is selected from hydrogen, halogen, optionally substituted C 1-4 alkyl, or optionally substituted C 1-4 alkoxy;
 R 4  is hydrogen; 
 R 5  is optionally substituted C 3-7 -heterocyclyl ring or is X—R 5a , wherein X is an optionally substituted C 2-6  alkylene chain and R 5a  is —N(R 5b ) 2 , wherein each occurrence of R 5b  is independently hydrogen or C 1-6  alkyl, or two occurrences of R 5b  taken together with the nitrogen atom to which they are bound, for an optionally substituted 3-7-membered heterocyclyl ring; and
 R 6  is hydrogen.