Il-8 receptor antagonists

Abstract

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

1 . A method of treating a chemokine mediated disease, wherein the chemokine binds to an IL-8α or β receptor in a mammal in need thereof, comprising administering to said mammal an effective amount of a compound which is:
 N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea; 
 N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′-(3-fluoro-2-methylphenyl)urea; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         2 . The method according to  claim 1  wherein the administration comprises N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. 
     
     
         3 . The method according to  claim 1  wherein the mammal is a human. 
     
     
         4 . The method according to  claim 1  wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, methane sulfonate, ethane sulfonate, acetate, malate, tartrate, citrate, lactate, oxalate, succinate, fumarate, maleate, benzoate, salicylate, phenylacetate, and mandelate. 
     
     
         5 . The method according to  claim 4  wherein the pharmaceutically acceptable salt is a hydrochloride salt. 
     
     
         6 . A method of treating psoriasis or atopic dermatitis in a human in need thereof, comprising administering to said human an effective amount of a compound which is:
 N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea;   N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′-(3-fluoro-2-methylphenyl)urea;   or a pharmaceutically acceptable salt thereof.   
     
     
         7 . The method according to  claim 6  wherein the administration comprises N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. 
     
     
         8 . The method according to  claim 6  wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, methane sulfonate, ethane sulfonate, acetate, malate, tartrate, citrate, lactate, oxalate, succinate, fumarate, maleate, benzoate, salicylate, phenylacetate, and mandelate. 
     
     
         9 . The method according to  claim 8  wherein the pharmaceutically acceptable salt is a hydrochloride salt. 
     
     
         10 . A method of treating a disease selected from the group consisting of osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, and ulcerative colitis in a human in need thereof, comprising administering to said human an effective amount of a compound which is N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea;
 N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′-(3-fluoro-2-methylphenyl)urea; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         11 . The method according to  claim 10  wherein the administration comprises N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. 
     
     
         12 . The method according to  claim 10  wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, methane sulfonate, ethane sulfonate, acetate, malate, tartrate, citrate, lactate, oxalate, succinate, fumarate, maleate, benzoate, salicylate, phenylacetate, and mandelate. 
     
     
         13 . The method according to  claim 12  wherein the pharmaceutically acceptable salt is a hydrochloride salt.