Treatment of duchenne muscular dystrophy

Abstract

There are disclosed compound of Formula (1): A 1 , A 2 , A 3 and A 4 which may be the same or different, represent N or CR 1 , X is a divalent group selected from O, S(O) n , C═W, NR 4 , NC(═O)R 5 and CR 6 R 7 , W is O, S, NR 20 , Y is N or CR 8 , one of R 4 , R 5 , R 6 , R 8 , R 9 and NR 20 represents -L-R 3 , in which L is a single bond or a linker group, additionally, R 1 , R 3 -R 9 , which may be the same or different, independently represent hydrogen or a substituent and R 20 represents hydrogen, hydroxyl, alkyl optionally substituted by aryl, alkoxy optionally substituted by aryl, aryl, CN, optionally substituted alkoxy, optionally substituted aryloxy, optionally substitute alkanoyl, optionally substituted aroyl, NO 2 , NR 30 R 31 , in which R 30 and R 31 , which may be the same or different, represent hydrogen, optionally substituted alkyl or optionally substituted aryl; additionally, one of R 30 and R 31 may represent optionally substituted alkanoyl or optionally substituted aroyl, n represents an integer from 0 to 2, in addition, when an adjacent pair of A 1 -A 4 each represent CR 1 , then the adjacent carbon atoms, together with their substituents may form a ring B, when X is CR 6 R 7 , R 6 and R 7 , together with the carbon atom to which they are attached may form a ring C, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the therapeutic and/or prophylactic treatment of Duchenne muscular dystrophy, Becker muscular dystrophy or cachexia.

1 - 38 . (canceled) 
     
     
         39 . A compound of general formula (Ia): 
       
         
           
           
               
               
           
         
         wherein
 R a  is methyl or ethyl; 
 R 9  is L-R 3 , in which L is a single bond; and 
 R 3  is optionally substituted aryl. 
 
       
     
     
         40 . The compound according to  claim 39  of formula Ib 
       
         
           
           
               
               
           
         
         wherein
 R 2  is halo; 
 R 2a  is hydrogen or halo; or 
 R 2a  and R 2 , together with the carbon atoms to which they are attached, form an optionally heterocyclic ring. 
 
       
     
     
         41 . The compound of  claim 39  wherein R a  is ethyl. 
     
     
         42 . The compound of  claim 40  wherein R 2a  and/or R 2  are selected from chloro and fluoro. 
     
     
         43 . The compound of  claim 40  wherein R a  is ethyl and R 2a  and/or R 2  are selected from chloro and fluoro. 
     
     
         44 . The compound of  claim 40  wherein R a  is ethyl and at least one of R 2a  and R 2  is chloro. 
     
     
         45 . The compound of  claim 41  of formula: 
       
         
           
           
               
               
           
         
         wherein R 2  is selected from fluoro and chloro; and 
         R 2a  is selected from hydrogen, fluoro and chloro. 
       
     
     
         46 . The compound of  claim 45  of formula: 
       
         
           
           
               
               
           
         
       
     
     
         47 . The compound of  claim 45  of formula: 
       
         
           
           
               
               
           
         
       
     
     
         48 . The compound of  claim 46  of formula 
       
         
           
           
               
               
           
         
       
     
     
         49 . The compound of  claim 40  of formula: 
       
         
           
           
               
               
           
         
         wherein R 2a  and R 2 , together with the ring to which they are attached, form naphthylene or quinoline. 
       
     
     
         50 . A pharmaceutical composition comprising a compound as defined in  claim 39  together with a pharmaceutically acceptable excipient. 
     
     
         51 . A pharmaceutical composition comprising a compound as defined in  claim 40  together with a pharmaceutically acceptable excipient. 
     
     
         52 . A method for the treatment of Duchenne muscular dystrophy or Becker muscular dystrophy in a subject having said disorder, comprising administering to the subject an effective amount of a compound as defined in  claim 39 . 
     
     
         53 . A method for the treatment of Duchenne muscular dystrophy or Becker muscular dystrophy in a subject having said disorder, comprising administering to the subject an effective amount of a compound as defined in  claim 40 . 
     
     
         54 . A method for the treatment of Duchenne muscular dystrophy or Becker muscular dystrophy in a subject having said disorder, comprising administering to the subject an effective amount of a composition as defined in  claim 50 . 
     
     
         55 . A method for the treatment of Duchenne muscular dystrophy or Becker muscular dystrophy in a subject having said disorder, comprising administering to the subject an effective amount of a composition as defined in  claim 51 .