Phthalazinone derivatives

Abstract

A compound of the formula (I): wherein: A and B together represent an optionally substituted, fused aromatic ring; X and Y are selected from CH and CH, CF and CH, CH and CF and N and CH respectively; R C is selected from H, C 1-4 alkyl; and R 1 is selected from C 1-7 alkyl, C 3-20 heterocyclyl and C 5-20 aryl, which groups are optionally substituted; or R C and R 1 together with the carbon and oxygen atoms to which they are attached form a spiro-C 5-7 oxygen-containing heterocyclic group, which is optionally substituted or fused to a C 5-7 aromatic ring.

1 - 15 . (canceled) 
     
     
         16 . A method for inhibiting the activity of PARP, comprising administering to a warm-blooded animal in need thereof an effective amount of a compound of the formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 A and B together represent an optionally substituted benzene ring; 
 X and Y are selected from CH and CH, CF and CH, CH and CF and N and CH respectively; 
 R C  is selected from H, C 1-4  and 
 R 1  is selected from C 1-7  alkyl, C 3-20  heterocyclyl and C 5-20  aryl, which groups are optionally substituted. 
 
     
     
         17 . (canceled) 
     
     
         18 . A method for treating cancer in a warm-blooded animal in need thereof, comprising administering a compound of the formula (I) 
       
         
           
           
               
               
           
         
       
       as an adjunct in cancer therapy or for potentiating tumour cells for treatment with ionizing radiation or chemotherapeutic agents, 
       wherein:
 A and B together represent an optionally substituted benzene ring; 
 X and Y are selected from CH and CH, CF and CH, CH and CF and N and CH respectively; 
 R C  is selected from H, C 1-4  alkyl; and 
 R 1  is selected from C 1-7  alkyl, C 3-20  heterocyclyl and C 5-20  aryl, which groups are optionally substituted. 
 
     
     
         19 . A method for treating cancer in an individual in need thereof, wherein said cancer is deficient in HR dependent DNA DSB repair pathway, said method comprising administering to the individual an effective amount of a compound of the formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 A and B together represent an optionally substituted benzene ring; 
 X and Y are selected from CH and CH, CF and CH, CH and CF and N and CH respectively; 
 R C  is selected from H, C 1-4  alkyl; and 
 R 1  is selected from C 1-7  alkyl, C 3-20  heterocvclyl and C 5-20  aryl, which groups are optionally substituted. 
 
     
     
         20 . The method according to  claim 19 , wherein said cancer comprises one or more cancer cells having a reduced or abrogated ability to repair DNA DSB by HR relative to normal cells. 
     
     
         21 . The method according to  claim 20 , wherein said cancer cells have a BRCA1 or BRCA2 deficient phenotype. 
     
     
         22 . The method according to  claim 21 , wherein said cancer cells are deficient in BRCA1 or BRCA2. 
     
     
         23 . The method according to  claim 19 , wherein said individual is heterozygous for a mutation in a gene encoding a component of the HR dependent DNA DSB repair pathway. 
     
     
         24 . The method according to  claim 23 , wherein said individual is heterozygous for a mutation in BRCA1 and/or BRCA2. 
     
     
         25 . The method according to  claim 19 , wherein said cancer is breast, ovary, pancreas or prostate cancer. 
     
     
         26 . The method according to  claim 19 , wherein said treatment further comprises administering ionising radiation or a chemotherapeutic agent.