Il-8 receptor antagonists

Abstract

This invention relates to novel compounds of Formula (I) to (VII), and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

1 . A compound selected from the group consisting of: 
 N-[4-chloro-2-hydroxy-3-(4-methyl-piperazine-1-sulfonyl)-phenyl]-N′-(2-chloro-3-fluorophenyl)urea;    N-[4-chloro-2-hydroxy-3-(4-(2-hydroxyethyl)-piperazine-1-sulfonyl)phenyl]-N′-(2-chloro-3-fluorophenyl)urea; and    N-[4-chloro-2-hydroxy-3-(1-piperazinylsulfonyl)phenyl]-N′-(2-chloro-3-fluorophenyl)urea    or a pharmaceutically acceptable salt thereof.    
   
   
       2 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier or diluent.  
   
   
       3 . A method of treating a chemokine mediated disease, wherein the chemokine binds to an IL-8 a or b receptor in a mammal, which method comprises administering to said mammal an effective amount of a compound according to  claim 1 .  
   
   
       4 . The method according to  claim 3  wherein the mammal is afflicted with a chemokine mediated disease selected from the group consisting of psoriasis, atopic dermatitis, arthritis (either oseo- or rheumatoid), asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome, inflammatory bowel disease, Crohn's disease, ulcerative colitis, stroke, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, cardiac and renal reperfusion injury, glomerulonephritis, thrombosis, graft vs. host reaction, alzheimers disease, allograft rejections, malaria, restinosis, angiogenesis, atherosclerosis, osteoporosis, gingivitis, viral diseases such as rhinovirus and undesired hematopoietic stem cell release.