Fatty acid modified forms of glucocorticoids

Abstract

Compounds are disclosed of the formula in which R 3 is C 8 to C 24 hydrocarbon or the residue of misoprostol. The compounds are useful for treating rhinitis and asthma, particularly by inhalation, and for treating inflammation, particularly by local or topical administration.

1 . A compound of Formula I:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  and R 2 , independently for each occurrence, represent a hydrogen, lower alkyl or lower acyl, or taken together R 1  and R 2  form a substituted or unsubstituted ketal;  
 R 3  is chosen from C 8  to C 24  hydrocarbon and  
                     
 R 4  is methyl or —OR 2 ; and  
 X and y are independently hydrogen or halogen.  
 
     
     
         2 . A compound according to  claim 1  of formula:  
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound according to  claim 2  of formula:  
       
         
           
           
               
               
           
         
       
     
     
         4 . A compound according to  claim 2  of formula  
       
         
           
           
               
               
           
         
       
     
     
         5 . A compound according to  claim 2  of formula  
       
         
           
           
               
               
           
         
       
     
     
         6 . A compound according to  claim 1  of formula:  
       
         
           
           
               
               
           
         
       
     
     
         7 . A compound according to  claim 4  wherein R 3  is the residue of phytanic acid:  
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound according to  claim 4  wherein R 3  is the residue of eicosapentaenoic acid  
       
         
           
           
               
               
           
         
       
     
     
         9 . A compound according to  claim 4  wherein R 3  is the residue of docosapentaenoic acid:  
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound according to  claim 4  wherein R 3  is the residue of docosahexaenoic acid:  
       
         
           
           
               
               
           
         
       
     
     
         11 . A pharmaceutical formulation for inhalation comprising a compound according to  claim 1  and a pharmaceutically acceptable fluid for solution or suspension.  
     
     
         12 . A pharmaceutical formulation according to  claim 11  additionally comprising a propellant.  
     
     
         13 . A method for treating bronchospasm comprising administering a compound of  claim 1 .  
     
     
         14 . A method for inducing bronchodilation comprising administering a compound of  claim 1 .  
     
     
         15 . A method for treating inflammatory conditions comprising administering a compound of  claim 1 .  
     
     
         16 . A method according to  claim 15  wherein said inflammatory condition is chronic obstructive pulmonary disease.  
     
     
         17 . A method according to  claim 15  wherein said inflammatory condition is asthma.  
     
     
         18 . A method according to  claim 15  wherein said inflammatory condition is rhinitis.  
     
     
         19 . A method according to  claim 15  wherein said compound is administered by inhalation.