Hydantoin derivatives useful as kv3 inhibitors

Abstract

said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.

What is claimed is: 
     
         1 . A method for the treatment of schizophrenia, which comprises administering to a subject in need thereof a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, C 1-4 alkyl, halo, haloC 1-4 alkyl, CN, C 1-4 alkoxy or haloC 1-4 alkoxy; 
         R 2  is H, C 1-4 alkyl, C 3-4  spiro carbocyclyl, haloC 1-4 alkyl or halo; 
         R 3  is H, C 1-4 alkyl, haloC 1-4 alkyl, halo; or R 3  is absent; 
         R 13  is H, C 1-4 alkyl, haloC 1-4 alkyl, halo; or R 13  is absent; 
         A is a 5 or 6 membered saturated or unsaturated heterocycle, with at least one O atom; which heterocycle is optionally fused with a cyclopropyl group to form a tricycle when considered together with the phenyl; 
         X is CH or N; 
         Y is CH or N; 
         R 4  is C 1-4  alkyl; 
         R 5  is H, Deuterium, C 1-4  alkyl; 
         or R 4  and R 5  can be fused to form C 3-4  spiro carbocyclyl; 
         wherein R 2  and R 3  may be attached to the same or a different ring atom; and wherein R 2  may be attached to a fused ring atom; 
         or a pharmaceutically acceptable salt and/or solvate thereof. 
       
     
     
         2 . The method according to  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, C 1-4 alkyl, halo, haloC 1-4 alkyl, CN, C 1-4 alkoxy or haloC 1-4 alkoxy; 
         R 2  is H, C 1-4 alkyl, C 3-4  spiro carbocyclyl, haloC 1-4 alkyl or halo; 
         R 3  is H, C 1-4 alkyl, haloC 1-4 alkyl, halo; 
         A is a 5 or 6 membered saturated or unsaturated heterocycle, with at least one O atom; which heterocycle is optionally fused with a cyclopropyl group to form a tricycle when considered together with the phenyl; 
         X is CH or N; 
         Y is CH or N; 
         R 4  is C 1-4  alkyl; 
         R 5  is H, Deuterium, C 1-4  alkyl; 
         or R 4  and R 5  can be fused to form C 3-4  spiro carbocyclyl; 
         wherein R 2  and R 3  may be attached to the same or a different ring atom; 
         and wherein R 2  may be attached to a fused ring atom; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . The method according to  claim 1 , wherein R 1  is H or methyl. 
     
     
         4 . The method according to  claim 1 , wherein A is a 5 membered saturated or unsaturated heterocycle, with at least one O atom; which heterocycle is optionally fused with a cyclopropyl group to form a tricycle when considered together with the phenyl. 
     
     
         5 . The method according to  claim 1 , wherein A is a 6 membered saturated or unsaturated heterocycle, with at least one O atom; which heterocycle is optionally fused with a cyclopropyl group to form a tricycle when considered together with the phenyl. 
     
     
         6 . The method according to  claim 4 , wherein the ring A contains one heteroatom. 
     
     
         7 . The method according to  claim 1 , wherein the ring A contains an oxygen in the meta position relative to the phenyl ring. 
     
     
         8 . The method according to  claim 1 , wherein the ring A is dihydrofuran or dihydropyran. 
     
     
         9 . The method according to  claim 1 , wherein the ring A is not fused with a cyclopropyl group. 
     
     
         10 . The method according to  claim 1 , wherein R 2  is H, F, methyl, ethyl, isopropyl or a C 3  spiro group. 
     
     
         11 . The method according to  claim 10 , wherein R 2  is H, methyl or a C 3  spiro group. 
     
     
         12 . The method according to  claim 1 , wherein R 3  is H, haloC 1-4 alkyl or halo. 
     
     
         13 . The method according to  claim 12 , wherein R 3  is H, F, methyl or ethyl. 
     
     
         14 . The method according to  claim 1 , wherein R 13  is H, haloC 1-4 alkyl or halo. 
     
     
         15 . The method according to  claim 1 , wherein R 13  is H, F or methyl, or is absent. 
     
     
         16 . The method according to  claim 1 , wherein R 4  is methyl or ethyl. 
     
     
         17 . The method according to  claim 1 , wherein R 5  is H or methyl. 
     
     
         18 . The method according to  claim 1 , wherein R 4  and R 5  have the stereochemical arrangement: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The method according to  claim 1 , wherein R 4  and R 5  together form a C 3-4  spiro carbocycle. 
     
     
         20 . A method for the treatment of schizophrenia, which comprises administering to a subject in need thereof a compound according to any one of Examples 1 to 70.