Fluoro substituted cycloalkanoindoles, compositions containing such compounds and methods of treatment

Abstract

Fluoro substituted cycloalkanoindole derivatives are antagonists of prostaglandins, and as such are useful for the treatment of prostaglandin mediated diseases.

What is claimed is:  
     
         1 . A compound of formula I:  
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof, wherein n is 0 or 1; m is 1, 2 or 3; R 1  is H, C 1 -C 3  alkyl, halogenated C 1 -C 3  alkyl or cyclopropyl; R 2  is 4-chlorophenyl or 2,4,6-trichlorophenyl.  
     
     
         2 . The compound of  claim 1  wherein n is 0.  
     
     
         3 . The compound of  claim 1  wherein n is 1.  
     
     
         4 . The compound of  claim 1  wherein m is 1.  
     
     
         5 . The compound of  claim 1  wherein m is 2.  
     
     
         6 . The compound of  claim 1  wherein R 1  is H.  
     
     
         7 . The compound of  claim 1  wherein R 1  is CH 3 .  
     
     
         8 . The compound of  claim 1  wherein R 2  is 4-chlorophenyl.  
     
     
         9 . The compound of  claim 1  wherein R 2  is 2,4,6-trichlorophenyl.  
     
     
         10 . The compound of  claim 1  having the stereoconfiguration shown below:  
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 10  wherein n is 0.  
     
     
         12 . The compound of  claim 10  wherein n is 1.  
     
     
         13 . The compound of  claim 10  wherein m is 1.  
     
     
         14 . The compound of  claim 10  wherein m is 2.  
     
     
         15 . The compound of  claim 10  wherein R 1  is H.  
     
     
         16 . The compound of  claim 10  wherein R 1  is CH 3 .  
     
     
         17 . The compound of  claim 10  wherein R 2  is 4-chlorophenyl.  
     
     
         18 . The compound of  claim 10  wherein R 2  is 2,4,6-trichlorophenyl.  
     
     
         19 . A compound selected from 
 [4-(4-chlorobenzyl)-7-fluoro-5-(methanesulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]-indol-3-yl]acetic acid,    {4-[1-(4-chlorophenyl)ethyl]-7-fluoro-5-methanesulfonyl-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl}acetic acid,    [9-(4-chlorobenzyl)-6-fluoro-8-methanesulfonyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl]-acetic acid, and    [4-(4-chlorobenzyl)-7-fluoro-5-methanesulfonyl-1-oxo-1,2,3,4-tetrahydro-cyclopenta-[b]indol-3-yl]acetic acid, or    a pharmaceutically acceptable salt thereof.    
     
     
         20 . The compound (3R)-[4-(4-chlorobenzyl)-7-fluoro-5-(methane-sulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid and pharmaceutically acceptable salts thereof.  
     
     
         21 . The compound (±)-4-[1-(4-chlorophenyl)ethyl]-7-fluoro-5-methanesulfonyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl}acetic acid and pharmaceutically acceptable salts thereof.  
     
     
         22 . The compound (±)-[9-(4-chlorobenzyl)-6-fluoro-8-methane-sulfonyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl]acetic acid and pharmaceutically acceptable salts thereof.  
     
     
         23 . The compound [4-(4-chlorobenzyl)-7-fluoro-5-methane-sulfonyl-1-oxo-1,2,3,4-tetrahydro-cyclopenta[b]indol-3-yl]acetic acid and pharmaceutically acceptable salts thereof.  
     
     
         24 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         25 . The composition of  claim 24  further comprising a second active ingredient selected from an antihistamine, a leukotriene antagonist and a leukotriene biosynthesis inhibitor.  
     
     
         26 . A method for the treatment of prostaglandin D2 mediated diseases which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of  claim 1 .  
     
     
         27 . A method for the treatment of nasal congestion which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of  claim 1 .  
     
     
         28 . A method for the treatment of allergic asthma which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of  claim 1 .  
     
     
         29 . A method for the treatment of allergic rhinitis which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of  claim 1.