Compounds for use in the treatment of cancer

Abstract

It is an aim of the present invention to provide inhibitors of human diphtheria toxin-like ADP-ribosyltransferases, such as ARTD10, for use as a medicine. It is another aim of the invention to provide compounds for use as human mono-ADP-ribosyltransferase (mARTD) inhibitors in vitro. In the present invention, it has been discovered that human ARTD10, which belongs to an enzyme family linked to cancer biology, can be specifically inhibited by the benzamide comprising compounds disclosed in the invention, such as 4,4′-oxydibenzamide.

What we claim is: 
     
         1 . A pharmaceutical composition comprising a compound having a general formula: 
       
         
           
           
               
               
           
         
         or a tautomer, stereoisomer or a pharmaceutically acceptable salt thereof, wherein: 
         the CLOSURE structure is absent and is replaced by a hydrogen atom on a carbon atom of the phenyl ring and by H 2  on the nitrogen atom of Formula(I); 
         L represents a linker of 1 or 2 linking atom(s) in a linear or in a branched conformation, and being selected from the group consisting of: C, O, N or S, wherein at least one of the linking atoms is oxygen (O); 
         R is a saturated or unsaturated cycloalkyl or an unsaturated heterocyclic ring system consisting of 1 heterocyclic ring, wherein said cycloalkyl or heterocyclic ring system optionally comprises at least one substituent selected from the group consisting of: H, F, Cl, Br, I, C 1-3  alkyl, halogen-substituted C 1-3  alkyl, C 1-3  alkoxy, halogen-substituted C 1-3  alkoxy, —CN, —OH, —COOH, —CONH 2  and —NO 2 ; 
         and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, filler, buffer, stabiliser, preservative or lubricant. 
       
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the linker L is selected from the group consisting of: O and O—CH 2 . 
     
     
         3 . The pharmaceutical composition according to  claim 1 , the compound having a formula 
       
         
           
           
               
               
           
         
         wherein: 
         the CLOSURE structure is absent and is replaced by a hydrogen atom on the phenyl ring and by H 2  on the nitrogen atom of Formula(II); 
         L represents a linker of 1 or 2 linking atom(s) in a linear or in a branched conformation, said atom(s) being selected from the group consisting of: C, O, N or S, wherein at least one of the linking atoms is oxygen (O); and 
         wherein R1 is optionally present on a 2, 3 or 4 position of the phenyl group and is selected from the group consisting of: H, F, Cl, Br, I, C 1-3  alkyl, halogen-substituted C 1-3  alkyl, C 1-3  alkoxy, halogen-substituted C 1-3  alkoxy, —CN, —OH, —COOH, —CONH 2  and —NO 2 . 
       
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein said compound is 4,4′-oxydibenzamide having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The pharmaceutical composition according to  claim 1 , said compound having the formula: 
       
         
           
           
               
               
           
         
         wherein the CLOSURE structure is absent and is replaced by a hydrogen atom on the phenyl ring and by H 2  on the nitrogen atom of Formula (IV) 
         wherein R1 is optionally present on a 2, 3 or 4 position of the phenyl group and represents a member selected from the group consisting of: H, F, Cl, Br, I, C 1-3  alkyl, halogen-substituted C 1-3  alkyl, C 1-3  alkoxy, halogen-substituted C 1-3  alkoxy, —CN, —OH, —COOH, —CONH 2  and —NO 2 , and 
         wherein the linker L of Formula (I) contains linking atoms A and B, and wherein A and B together represent linkers selected from O—CH 2 , CH 2 —O, O—C(═O) or C(═O)—O. 
       
     
     
         6 . The pharmaceutical composition according to  claim 5 , said compound having the formula: