CCR1 antagonists and methods of use therefor

Abstract

The invention provides compounds having the formula: wherein R 1 is halogen. The invention also provides compositions comprising the compounds, and methods of treating diseases or disorders that comprise administering one or more of the compounds to a subject in need thereof. The disclosed compounds have CCR1 antagonist activity.

What is claimed is:  
     
         1 . A compound having the formula:  
       
         
           
           
               
               
           
         
         or a physiologically acceptable salt thereof, wherein R 1  is a halogen.  
       
     
     
         2 . The compound of  claim 1  wherein R 1  is selected from the group consisting of chloro, fluoro and bromo.  
     
     
         3 . The compound of  claim 2  wherein R 1  is chloro.  
     
     
         4 . A pharmaceutical composition comprising the compound of  claim 1  and a physiologically acceptable carrier or excipient.  
     
     
         5 . A method for treating a disease characterized by pathogenic leukocyte recruitment, pathogenic leukocyte activation or pathogenic leukocyte recruitment and activation, comprising administering to a subject in need thereof an effective amount of a compound of  claim 1 .  
     
     
         6 . A compound having the structure:  
       
         
           
           
               
               
           
         
         or a physiologically acceptable salt thereof, wherein R 1  is a halogen.  
       
     
     
         7 . The compound of  claim 6  wherein R 1  is selected from the group consisting of chloro, fluoro and bromo.  
     
     
         8 . The compound of  claim 7  wherein R 1  is chloro.  
     
     
         9 . A pharmaceutical composition comprising the compound of  claim 6  and a physiologically acceptable carrier or excipient.  
     
     
         10 . A method for treating a disease characterized by pathogenic leukocyte recruitment, pathogenic leukocyte activation or pathogenic leukocyte recruitment and activation, comprising administering to a subject in need thereof an effective amount of a compound of  claim 6 .  
     
     
         11 . The method of  claim 10  wherein R 1  chloro.  
     
     
         12 . The method of  claim 10  wherein said disease is an acute or chronic inflammatory disease.  
     
     
         13 . The method of  claim 10  wherein said disease is selected from the group consisting of inflammatory arthritis, inflammatory demyelinating disease, atherosclerosis, arteriosclerosis, restenosis, ischemia/reperfusion injury, diabetes mellitus, psoriasis, inflammatory bowel diseases, rejection of a transplanted graft, graft versus host disease, allergy and asthma.  
     
     
         14 . The method of  claim 13  wherein said disease is inflammatory arthritis.  
     
     
         15 . The method of  claim 14  wherein said inflammatory arthritis is rheumatoid arthritis.  
     
     
         16 . The method of  claim 13  wherein said disease is inflammatory demyelinating disease.  
     
     
         17 . The method of  claim 16  wherein said inflammatory demyelinating disease is multiple sclerosis.  
     
     
         18 . A method of antagonizing a C—C Chemokine Receptor 1 in a subject, comprising administering to a subject in need thereof an effective amount of a compound of  claim 1 .  
     
     
         19 . A compound having the formula:  
       
         
           
           
               
               
           
         
         or a physiologically acceptable salt thereof, wherein R 1  is a halogen.  
       
     
     
         20 . A pharmaceutical composition comprising the compound of  claim 19  and a physiologically acceptable carrier or excipient.