Novel compounds and methods for treating multiple sclerosis

Abstract

This invention provides novel thiomorpholinone compounds useful for treating multiple sclerosis.

We claim:  
     
         1 . A compound of the formula I  
                   
       wherein: 
 R 1  and R 2  are each independently selected from C 1 -C 8  alkyl; C 2 -C 8  alkenyl; C 2 -C 8  alkynyl; C 1 -C 8  alkyloxy; C 1 -C 8  alkylthio; trifluoromethyl; C 1 -C 4  alkyl substituted with phenyl; phenyl; F; Cl; NO 2 ; phenoxy; C 1 -C 4  alkyl substituted with phenoxy; thiophenyl; C 1 -C 4  alkylthiophenyl; —COOR 7 ; —N(R 7 ) 2  or —N(R 7 )SO 2 R 7  where each R 7  is independently hydrogen or C 1 -C 6  alkyl;  
 R 3  is H or C 1 -C 4  alkyl;  
 R 4  and R 5  are each individually H, or when taken together form a bond;  
 R 6  is H; C 1 -C 8  alkyl; C 2 -C 8  alkenyl; C 2 -C 8  alkynyl; —SO 2 CH 3 ; —(CH 2 ) n NR 8 R 9 ; —(CH 2 ) n CO 2 R 8 ; —(CH 2 ) n OR 8  where n is an integer from 1 to 6, both inclusive, and R 8  and R 9  are each independently hydrogen; C 1 -C 6  alkyl; C 2 -C 6  alkenyl; C 2 -C 6  alkynyl; phenyl; C 1 -C 4  alkyl substituted with phenyl; —(CH 2 ) q OH; or (CH 2 ) q S(C 1 -C 4 alkyl) where q is an integer from 2 to 6, both inclusive; and  
 X is  
                 
 
 where m is 0 or 1;  
 or a pharmaceutically acceptable salt or optical isomer thereof.  
 
     
     
         2 . The compound of    claim 1    wherein R 6  is hydrogen, C 1 -C 6  alkyl C 2 -C 6  alkenyl or —(CH 2 ) n OR 8  where n is 2 and R 8  is hydrogen; X is  
                 
 
       where m is 0; and R 1  and R 2  are each independently selected from C 1 -C 8  alkyl or C 1 -C 8  alkoxy.  
     
     
         3 . A compound of    claim 1    which is 2-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]-4-methyl-3-thiomorpholinone.  
     
     
         4 . A compound of    claim 1    which is (−)2-[[3,5-bis(1,1-dimethyl ethyl)-4-hydroxy phenyl]methyl]-4-methyl-3-thiomorpholinone.  
     
     
         5 . A method for treating multiple sclerosis in a mammal in need of such treatment which comprises administering to said mammal a therapeutically effective amount of a compound of formula I as claimed in any one of    claims 1    to    4   .  
     
     
         6 . A pharmaceutical formulation comprising a compound of formula I as claimed in any one    claims 1    to    4    together with a pharmaceutically acceptable carrier or diluent therefor.  
     
     
         7 . The use of a compound of formula I as claimed in any one of    claims 1    to    4    for the manufacture of a medicament for treating multiple sclerosis in a mammal.