Prodrugs of a piperidinyl derivative as modulators of chemokine receptor activity

Abstract

The present application describes prodrugs of the compound of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis using the prodrug compounds of the invention are disclosed.

What is claimed is: 
     
         1 . A compound of the formula 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt form thereof. 
     
     
         2 . A compound of the formula 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt form thereof. 
     
     
         3 . A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more of the compounds of  claim 1 . 
     
     
         4 . A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more of the compounds of  claim 2 . 
     
     
         5 . A method for modulation of chemokine or chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of  claim 1 . 
     
     
         6 . The method of  claim 5 , wherein the chemokine or chemokine receptor activity is CCR-1 or CCR-1 receptor activity. 
     
     
         7 . A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of  claim 1 ; wherein said disorder is selected from osteoarthritis, aneurysm, fever, cardiovascular effects, Crohn's disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, neuropathic pain, inflammatory bowel disease, alveolitis, ulcerative colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerulonephritis, asthma, multiple sclerosis, atherosclerosis, rheumatoid arthritis, restenosis, organ transplantation, multiple myeloma, colorectal cancer, hepatocellular cancer and other cancers. 
     
     
         8 . A method for treating inflammatory diseases comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of  claim 1 . 
     
     
         9 . A method for preparing a medicament for the treatment of osteoarthritis, aneurysm, fever, cardiovascular effects, Crohn's disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, neuropathic pain, inflammatory bowel disease, alveolitis, ulcerative colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerulonephritis, asthma, multiple sclerosis, atherosclerosis, and rheumatoid arthritis comprising formulating one or more of the compounds of  claim 1 . 
     
     
         10 . A method for treating a patient in need of therapy comprising administering to said patient in need thereof a therapeutically effective amount of one or more of the compounds of  claim 1 . 
     
     
         11 . A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of a composition of  claim 3 , wherein said disorder is selected from osteoarthritis, aneurysm, fever, cardiovascular effects, Crohn's disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, neuropathic pain, inflammatory bowel disease, alveolitis, ulcerative colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerulonephritis, asthma, multiple sclerosis, atherosclerosis, rheumatoid arthritis, restenosis, organ transplantation, multiple myeloma, colorectal cancer, hepatocellular cancer and other cancers. 
     
     
         12 . A method for treating inflammatory diseases comprising administering to a patient in need thereof a therapeutically effective amount of a composition of  claim 3 . 
     
     
         13 . A method for preparing a medicament for the treatment of osteoarthritis, aneurysm, fever, cardiovascular effects, Crohn's disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, neuropathic pain, inflammatory bowel disease, alveolitis, ulcerative colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerulonephritis, asthma, multiple sclerosis, atherosclerosis, and rheumatoid arthritis comprising formulating a composition of  claim 3  into a useful pharmaceutical dosage-form. 
     
     
         14 . A method for treating a patient in need of therapy comprising administering to said patient in need thereof a therapeutically effective amount of a composition of  claim 3 .