Pyrrolopyrazone inhibitors of tankyrase

Abstract

There are provided compounds of the formula wherein R 1 and R 2 are as described herein. The compounds are useful as anticancer agents.

We claim: 
     
         1 . A compound of the formula wherein 
       
         
           
           
               
               
           
         
         R 1  is selected from the group consisting of C 1-6  alkyl, halo, cyano, C 1-6  hydroxyalkyl, 
       
       
         
           
           
               
               
           
         
         R 2  is (i)aryl (ii)heteroaryl said aryl or heteroaryl optionally substituted by one or three groups independently selected from C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl or halogen and said heteroaryl is pyridinyl, (iii) piperazinyl or (iv) piperidinyl said piperazinyl or piperidinyl optionally substituted by aryl which aryl is optionally substituted as described above; or, a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound of  claim 1  wherein
 R 2  is 
 
       
         
           
           
               
               
           
         
         A is CH or N; 
         R 3  is optionally substituted aryl; and, 
         R 4  is trifluoromethyl or methoxy. 
       
     
     
         3 . The compound of  claim 1  wherein R 2  is optionally substituted pyridinyl. 
     
     
         4 . A compound of  claim 1  selected from the group consisting of
 6-Bromo-3-(4-methoxy-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one, 
 1-Oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carbonitrile, 
 N-Hydroxy-1-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carboxamidine, 
 1-Oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carboxylic acid amide, 
 1-Oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carboxamidine, 
 6-(4,5-Dihydro-1H-imidazol-2-yl)-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one, 
 6-Methyl-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one, 
 6-Hydroxymethyl-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one, 
 3-[4-(2-Fluoro-phenyl)-piperazin-1-yl]-6-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one and 
 6-Bromo-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one. 
 
     
     
         5 . A compound according to  claim 1  for use as therapeutically active substance. 
     
     
         6 . A pharmaceutical composition comprising a compound according to  claim 1  and a therapeutically inert carrier. 
     
     
         7 . The use of a compound according to  claim 1  for the treatment of cancer. 
     
     
         8 . The use of a compound according to  claim 1  for the preparation of a medicament for the treatment of cancer. 
     
     
         9 . A method for the treatment of cancer, which method comprises administering an effective amount of a compound as defined in  claim 1 .