Non-Steroidal Glucocorticoid Inhibitors and Their Use in Treating Inflammation, Allergy and Auto-Immune Conditions

Abstract

The present invention provides compounds of formula (I): a process for their preparation, to pharmaceutical compositions comprising the compounds and the preparation of said compositions, to intermediates and to use of the compounds for the manufacture of a medicament for therapeutic treatment, particularly for the treatment of inflammation, allergy and/or auto-immune conditions.

1 . A method for the treatment of a human or animal subject with an inflammatory and/or allergic condition which method comprises administering to said human or animal subject an effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen; 
         R 2  and R 3  are each independently selected from bromine, chlorine, fluorine, —CHF 2 , —CF 3  and —OCHF 2 , or R 2  is —SO 2 CH 3  and R 3  is hydrogen; 
         n is an integer selected from 0, 1 and 2, 
         when n is 1, X is selected from chlorine and fluorine, and 
         when n is 2, each X is fluorine; 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A method for the treatment of a human or animal subject with ophthalmic inflammation, which method comprises administering to said human or animal subject an effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen; 
         R 2  and R 3  are each independently selected from bromine, chlorine, fluorine, —CHF 2 , —CF 3  and —OCHF 2 , or R 2  is —SO 2 CH 3  and R 3  is hydrogen; 
         n is an integer selected from 0, 1 and 2, 
         when n is 1, X is selected from chlorine and fluorine, and 
         when n is 2, each X is fluorine; 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of treatment as claimed in  claim 1 , which method comprises administering to said human or animal subject an effective amount of a compound which is: 5-amino-N-[2-({[(2,6-dichlorophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (Enantiomer 2) as the free base; or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The method of treatment as claimed in  claim 2 , which method comprises administering to said human or animal subject an effective amount of a compound which is: 5-amino-N-[2-({[(2,6-dichlorophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (Enantiomer 2) as the free base; or a pharmaceutically acceptable salt thereof.