N-ureidoalkyl-piperidines as modulators of chemokine receptor activity

Abstract

The present application describes N-ureidoalkyl piperidines as modulators of chemokine receptors, or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

1 . A compound of formula (I):  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt form thereof, wherein 
 R 1  is selected from methyl; and  
 R 2  is selected from H, methyl, and ethyl.  
 
   
   
       2 . A compound of claims  1 , wherein 
 R 2  is H.    
   
   
       3 . A compound of claims  1 , wherein 
 R 2  is methyl.    
   
   
       4 . A compound of claims  1 , wherein 
 R 2  is ethyl.    
   
   
       5 . A compound of  claim 1  or a pharmaceutically acceptable salt, wherein the compound is selected from: 
 N-[3-ethyl-5-(1-methyl-1H-tetraazol-5-yl)phenyl]-N′-{(1R,2S)-3-[(3S)-3-(4-fluorobenzyl)-1-piperidinyl]-2-hydroxy-1-methylpropyl}urea;    N-{(1R,2S)-3-[(3S)-3-(4-fluorobenzyl)-1-piperidinyl]-2-hydroxy-1-methylpropyl}-N′-[3-(1-methyl-1H-tetraazol-5-yl)phenyl]urea; and    N-{(1R,2S)-3-[(3S)-3-(4-fluorobenzyl)-1-piperidinyl]-2-hydroxy-1-methylpropyl}-N′-[3-methyl-5-(1-methyl-1H-tetraazol-5-yl)phenyl]urea.    
   
   
       6 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof.  
   
   
       7 . A method for modulation of chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to  claim 1 .  
   
   
       8 . A method for treating asthma, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to  claim 1 .  
   
   
       9 . The method of  claim 7  wherein modulation of chemokine receptor activity comprises contacting a CCR3 receptor with an effective inhibitory amount of the compound.  
   
   
       10 . A method for treating inflammatory disorders comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof.  
   
   
       11 . A method for treating disorders, wherein the disorder is selected from asthma, allergic rhinitis, atopic dermatitis, inflammatory bowel diseases, idiopathic pulmonary fibrosis, bullous pemphigoid, helminthic parasitic infections, allergic colitis, eczema, conjunctivitis, transplantation, familial eosinophilia, eosinophilic cellulitis, eosinophilic pneumonias, eosinophilic fasciitis, eosinophilic gastroenteritis, drug induced eosinophilia, HIV infection, cystic fibrosis, Churg-Strauss syndrome, lymphoma, Hodgkin's disease, and colonic carcinoma.  
   
   
       12 . The method according to  claim 11 , wherein the disorder is selected from asthma, allergic rhinitis, atopic dermatitis, and inflammatory bowel diseases.  
   
   
       13 . The method according to  claim 12 , wherein the disorder is asthma.