Heterocyclyl-3-sulfonylindazoles as 5-hydroxytryptamine-6 ligands

Abstract

The present invention provides a compound of formula I and the use thereof in the therapeutic treatment of disorders related to or affected by the 5-HT6 receptor.

1 . A method for the treatment of a central nervous system disorder related to or affected by the 5-HT6 receptor in a patient in need thereof which comprises providing to said patient a therapeutically effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
       
       wherein
 A is C, CR 8  or N; 
 R 1  is H, halogen, CN, COR 9 , OCO 2 R 10 , CO 2 R 11 , CONR 12 R 13 , SO x R 14 , NR 15 R 16 , OR 17  or a C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl or heteroaryl group each optionally substituted; 
 R 2  is an optionally substituted C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, or heteroaryl group or an optionally substituted 8- to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S; 
 R 3  is H or a C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl or heteroaryl group each optionally substituted; 
 R 4  is H or a C 1 -C 6 alkyl or C 3 -C 7 cycloalkyl group each optionally substituted; 
 R 5 , R 6  and R 7  are each independently H or a C 1 -C 6 alkyl or C 3 -C 7 cycloalkyl group each optionally substituted; 
 m and p are each independently an integer of 1, 2 or 3; 
 n is an integer of 1 or 2; 
 R 8  is H, OH or an optionally substituted C 1 -C 6 alkoxy group; 
 R 9 , R 10 , R 11  and R 17  are each independently H or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; 
 R 12 , R 13 , R 15  and R 16  are each independently H or an optionally substituted C 1 -C 4 alkyl group or R 12  and R 13  or R 15  and R 16  may be taken together with the atom to which they are attached to form a 5- to 7-membered ring optionally containing another heteroatom selected from O, NR 18  or SO x ; 
 R 14  is a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; 
 R 18  is H or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, cycloheteroalkyl, aryl or heteraryl group each optionally substituted; 
 x is 0 or an integer of 1 or 2; and 
    represents a single bond or a double bond; or 
 
       the stereoisomes thereof or the pharmaceutically acceptable salts thereof. 
     
     
         2 . The method according to  claim 1  wherein said disorder is a motor disorder, anxiety disorder or cognitive disorder. 
     
     
         3 . The method according to  claim 1  wherein said disorder is a neurodegenerative disorder. 
     
     
         4 . The method according to  claim 2  wherein said disorder is selected from the group consisting of: attention deficit disorder; obsessive compulsive disorder; withdrawal from drug, alcohol or nicotine addiction; schizophrenia; depression; and Alzheimer's disease. 
     
     
         5 . The method according to  claim 3  wherein said disorder is selected from the group consisting of: stroke; head trauma; and neuropathic pain.