Benzenesulfonic acid indol-5-yl esters as antagonists of the 5-ht6 receptor

Abstract

The present invention relates to compounds of formula I: which are antagonists of 5-HT6 receptor.

1 .- 14 . (canceled)  
   
   
       15 . A method of treating cognitive disorders comprising: administering to a patient in need thereof an effective amount of a compound of the formula  
     
       
         
         
             
             
         
       
     
     wherein 
 R is hydrogen C 1  -C 6  alkyl, or C 3 -C 6  cycloalkyl; 
 which C 1 -C 6  alkyl is unsubstituted or is substituted with 1 or 2 substituents selected from the group consisting of C 3 -C 6  cycloalkyl phenyl, substituted phenyl, pyridyl, and trifluoromethyl; 
 which phenyl is unsubstituted or is substituted with 1 to 3 groups independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halogen, cyano, trifluoromethyl, nitro, and phenyl;  
 
 
 R 1  is hydrogen or C 1  -C 3  alkyl  
 R 2  is hydrogen or C 1 -C 6  alkyl;  
 R 3  is hydrogen or halo;  
 R 4  is hydrogen, C 1  -C 6  alkyl, vinyl, allyl, C 9 -C 6  alkynyl, or halo;  
 X is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, C 1 -C 6  alkoxy, nitro, amino, C 1 -C 6  alkylsulfonylamino, and cyano, or X is 5 halo substituents;  
   represents either a single or a double bond;  
 or a pharmaceutically acceptable addition salt thereof.  
 
   
   
       16 . A method of treating Alzheimer's disease, comprising: administering to a patient in need thereof an effective amount of a compound of the formula  
     
       
         
         
             
             
         
       
     
     wherein 
 R is hydrogen, C 1 -C 6  alkyl or C 3 -C 6  cycloalkyl; 
 which C 1 -C 6  alkyl is unsubstituted or is substituted with 1 or 2 substituents selected from the group consisting of C 3 -C 6  cycloalkyl, phenyl, substituted phenyl, pyridyl, and trifluoromethyl; 
 which phenyl is unsubstituted or is substituted with 1 to 3 groups independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl C 1 -C 6  alkoxy, halogen, cyano, trifluoromethyl, nitro, and phenyl;  
 
 
 R 1  is hydrogen or C 1 -C 3  alkyl  
 R 2  is hydrogen or C 1 -C 6  alkyl;  
 R 3  is hydrogen or halo;  
 R 4  is hydrogen, C 1 -C 6  alkyl, vinyl, allyl, C 2 -C 6  alkynyl, or halo;  
 X is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, C 1  alkyl, C 1 -C 6  alkoxy, nitro, amino, C 1 -C 6  alkylsulfonylamino, and cyano, or X is 5 halo substituents;  
   represents either a single or a double bond;  
 or a pharmaceutically acceptable addition salt thereof.  
 
   
   
       17 . A method of treating schizophrenia, comprising: administering to a patient in need thereof an effective amount of a compound of the formula  
     
       
         
         
             
             
         
       
     
     wherein 
 R is hydrogen, C 1 -C 6  alkyl or C 3 -C 6  cycloalkyl; 
 which C 1 -C 6  alkyl is unsubstituted or is substituted with 1 or 2 substituents selected from the group consisting of C 3 -C 6  cycloalkyl, phenyl, substituted phenyl, pyridyl, and trifluoromethyl; 
 which phenyl is unsubstituted or is substituted with 1 to 3 groups independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halogen, cyano, trifluoromethyl, nitro, and phenyl;  
 
 
 R 1  is hydrogen or C 1 -C 3  alkyl  
 R 2  is hydrogen or C 1 -C 6  alkyl;  
 R 3  is hydrogen or halo;  
 R 4  is hydrogen, C 1 -C 6  alkyl, vinyl, allyl, C 2 -C 6  alkynyl, or halo;  
 X is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, nitro, amino, C 1 -C 6  alkylsulfonylamino, and cyano, or X is 5 halo substituents;  
   represents either a single or a double bond;  
 or a pharmaceutically acceptable addition salt thereof.  
 
   
   
       18 .- 22 . (canceled)  
   
   
       23 . A method of  claim 16  wherein the compound is 2,6-Difluorobenzenesulfonic acid 1-methyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester, or a pharmaceutically acceptable salt thereof.  
   
   
       24 . A method of  claim 17  wherein the compound is 2,6-Difluorobenzenesulfonic acid 1-methyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester, or a pharmaceutically acceptable salt thereof.  
   
   
       25 . A method of treating migraine, comprising: administering to a patient in need thereof an effective amount of a compound of the formula  
     
       
         
         
             
             
         
       
     
     wherein 
 R is hydrogen, C 1 -C 6  alkyl, or C 3 -C 6  cycloalkyl; 
 which C 1 -C 6  alkyl is unsubstituted or is substituted with 1 or 2 substituents selected from the group consisting of C 3 -C 6  cycloalkyl, phenyl, substituted phenyl, pyridyl, and trifluoromethyl; 
 which phenyl is unsubstituted or is substituted with 1 to 3 groups independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halogen, cyano, trifluoromethyl, nitro, and phenyl;  
 
 
 R 1  is hydrogen or C 1 -C 3  alkyl  
 R 2  is hydrogen or C 1 -C 6  alkyl;  
 R 3  is hydrogen or halo;  
 R 4  is hydrogen, C 1 -C 6  alkyl, vinyl, allyl, C 2 -C 6  alkynyl, or halo;  
 X is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, nitro, amino, C 1 -C 6  alkylsulfonylamino, and cyano, or X is 5 halo substituents;  
   represents either a single or a double bond;  
 or a pharmaceutically acceptable addition salt thereof.  
 
   
   
       26 . A method of  claim 25  wherein the compound is 2,6-Difluorobenzenesulfonic acid 1-methyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester, or a pharmaceutically acceptable salt thereof.  
   
   
       27 . A method of treating anxiety, comprising: 
 administering to a patient in need thereof an effective amount of a compound of the formula                          wherein    R is hydrogen, C 1 -C 6  alkyl, or C 3 -C 6  cycloalkyl; 
 which C 1 -C 6  alkyl is unsubstituted or is substituted with 1 or 2 substituents selected from the group consisting of C 3 -C 6  cycloalkyl, phenyl, substituted phenyl, pyridyl, and trifluoromethyl; 
 which phenyl is unsubstituted or is substituted with 1 to 3 groups independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halogen, cyano, trifluoromethyl, nitro, and phenyl;  
 
   R 1  is hydrogen or C 1 -C 3  alkyl    R 2  is hydrogen or C 1 -C 6  alkyl;    R 3  is hydrogen or halo;    R 4  is hydrogen, C 1 -C 6  alkyl, vinyl, allyl, C 2 -C 6  alkynyl, or halo;    X is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, nitro, amino, C 1 -C 6  alkylsulfonylamino, and cyano, or X is 5 halo substituents;      represents either a single or a double bond;    or a pharmaceutically acceptable addition salt thereof.    
   
   
       28 . A method of  claim 27  wherein the compound is 2,6-Difluorobenzenesulfonic acid 1-methyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester, or a pharmaceutically acceptable salt thereof.