Piperdine Derivatives as CCR5 Inhibitors

Abstract

Disclosed are compounds of formula I: wherein R 1 , R 2 , R 3 and X are as defined herein, in free or salt form, which are useful as CCR5 inhibitors, e.g. in the prevention or treatment of disorders mediated by interactions between chemokine receptors and their ligands.

1 - 8 . (canceled) 
     
     
         9 . A compound of formula I 
       
         
           
           
               
               
           
         
       
       wherein
 a) R 2  is a residue of formula 
 
       
         
           
           
               
               
           
         
         wherein
 i) R 1  is phenyl, X is a direct bond and R 3  is pyridyl 
 or 
 ii) R 1  is pyridyl, X is a direct bond and R 3  is phenyl 
 
         or 
         b) R 2  is a residue of formula 
       
       
         
           
           
               
               
           
         
         wherein Y is —C═ or —N═ 
         and 
         R 1  is pyridyl, X is a direct bond and R 3  is phenyl, 
         or 
         c) R 2  is a residue of formula 
       
       
         
           
           
               
               
           
         
         X is a direct bond and one of R 1  and R 3  is phenyl and the other is pyridyl, 
         or 
         d) R 2  is a residue of formula 
       
       
         
           
           
               
               
           
         
         R 1  is pyridyl, X is a direct bond and R 3  is phenyl, 
         or 
         e) R 2  is indol-4-yl, R 1  is pyridyl, X is a direct bond and R 3  is phenyl, 
         in free form or in salt form. 
       
     
     
         10 . A compound of formula I as defined in claim  1  or a pharmaceutically acceptable salt thereof for use as a pharmaceutical. 
     
     
         11 . A pharmaceutical composition comprising a compound of formula I as defined in claim  1  or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable diluent or carrier therefor. 
     
     
         12 . A method of preventing or treating a disorder or disease comprising administering to a subject in need thereof the compound of formula I as defined in claim  1  or a pharmaceutically acceptable salt thereof, wherein said disorder or disease is selected from the group consisting transplantation, acute or chronic rejection of organ, tissue or cell allow or xenografts or delayed graft function, autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or II and the disorders associated therewith, vasculitis, pernicious anemia, Sjoegren syndrome, uveitis, psoriasis, alopecia areata and others, allergic diseases, allergic asthma, atopic dermatitis, allergic rhinitis/conjunctivitis, allergic contact dermatitis, inflammatory diseases optionally with underlying aberrant reactions, inflammatory bowel disease, Crohn's disease or ulcerative colitis, intrinsic asthma, inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, atherosclerosis, osteoarthritis, irritant contact manifestations of immunologically-mediated disorders, inflammatory eye disease, keratoconjunctvits, myocarditis or hepatitis, ischemia/reperfusion injury, myocardial infarction, stroke, gut ischemia, renal failure or hemorrhage shock, traumatic shock, cancer, solid tumors or lymphatic cancer, T cell lymphomas or T cell leukemias, metastasizing or angiogenesis, infectious diseases, toxic shock, septic shock, adult respiratory distress syndrome, and viral infections. 
     
     
         13 . A pharmaceutical combination comprising a) a first agent which is a compound of formula I as defined in claim  1 , in free form or in pharmaceutically acceptable salt form, and b) at least one co-agent.