Method of treatment of shwachman-diamond syndrome

Abstract

The invention relates to compounds for the treatment of ribosomopathies. In particular, it refers to compounds for the treatment of Shwachman-Diamond Syndrome (SDS) and other ribosomopathies, such as Diamond-Blackfan Anemia (DBA), X-linked dyskeratosiscongenita (DKC) and Treacher Collins syndrome (TCS).

1 . A method for the treatment of a ribosomopathy comprising administering to a subject in need thereof of a therapeutically effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
         Wherein Z is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocycle, substituted or unsubstituted arylalkyl; 
         R 1  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —(CH 2 CH 2 ) n OR 6  or any biohydrolyzable group; 
         R 2 , R 3 , R 4 , R 5  and R 6  are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, alkoxy, aryloxy, heteroaryloxy, halogen, CF 3 , OCF 3 , OCHF 2 , CM, COOH, COOR 7 , SO 2 R 7 , NO 2 , NH 2 , or N(R 7 ) 2 ; 
         each occurrence of R 7  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, alkoxy, aryloxy, heteroaryloxy, halogen or CF 3 ; 
         n is an integer from 1 to 7. 
       
     
     
         2 . The method for the treatment according to  claim 1 , wherein said compound is of formula (II) 
       
         
           
           
               
               
           
         
         wherein Z is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocycle, substituted or unsubstituted arylalkyl; and R is hydrogen or halogen. 
       
     
     
         3 . The method for the treatment according to  claim 2 , wherein said compound is a compound of formula (II), Z is substituted or unsubstituted aryl and R is hydrogen or halogen. 
     
     
         4 . The method for the treatment according to  claim 1 , wherein said compound is Ataluren of formula 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method for the treatment according to  claim 1 , wherein said ribosomopathy is selected from the group consisting of Shwachman-Diamond Syndrome (SDS), Diamond-Blackfan Anemia (DBA), X-linked dyskeratosis congenita (DKC) and Treacher Collins syndrome (TCS). 
     
     
         6 . The method for the treatment according  claim 1 , wherein said ribosomopathy is Shwachman-Diamond Syndrome (SDS). 
     
     
         7 . A method for the treatment of a ribosomopathy comprising administering a pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier to a subject in need thereof. 
     
     
         8 . The method for the treatment according to  claim 7 , wherein said ribosomopathy is selected from the group consisting of Shwachman-Diamond Syndrome (SDS), Diamond-BlackfanAnemia (DBA), X-linked dyskeratosis congenita (DKC) and Treacher Collins syndrome (TCS). 
     
     
         9 . The method for the treatment according to  claim 7 , wherein said ribosomopathy is Shwachman-Diamond Syndrome (SDS).